diff --git a/src/compiler/checker.ts b/src/compiler/checker.ts
index 11ac767e5aeb3..0536d79ad7bde 100644
--- a/src/compiler/checker.ts
+++ b/src/compiler/checker.ts
@@ -18713,7 +18713,8 @@ m2: ${(this.mapper2 as unknown as DebugTypeMapper).__debugToString().split("\n")
                 // Before normalization: if `source` is type an object type, and `target` is primitive,
                 // skip all the checks we don't need and just return `isSimpleTypeRelatedTo` result
                 if (originalSource.flags & TypeFlags.Object && originalTarget.flags & TypeFlags.Primitive) {
-                    if (isSimpleTypeRelatedTo(originalSource, originalTarget, relation, reportErrors ? reportError : undefined)) {
+                    if (relation === comparableRelation && !(originalTarget.flags & TypeFlags.Never) && isSimpleTypeRelatedTo(originalTarget, originalSource, relation) ||
+                        isSimpleTypeRelatedTo(originalSource, originalTarget, relation, reportErrors ? reportError : undefined)) {
                         return Ternary.True;
                     }
                     if (reportErrors) {
diff --git a/tests/baselines/reference/discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.symbols b/tests/baselines/reference/discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.symbols
new file mode 100644
index 0000000000000..31aef77dba10e
--- /dev/null
+++ b/tests/baselines/reference/discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.symbols
@@ -0,0 +1,88 @@
+=== tests/cases/compiler/discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts ===
+// strictNullChecks: false
+
+// repro #49643
+
+interface A {}
+>A : Symbol(A, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 0, 0))
+
+interface B {}
+>B : Symbol(B, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 4, 14))
+
+declare let opts:
+>opts : Symbol(opts, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 7, 11))
+
+   | { objectRef?: undefined; getObjectRef: () => any }
+>objectRef : Symbol(objectRef, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 8, 6))
+>getObjectRef : Symbol(getObjectRef, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 8, 29))
+
+   | { objectRef: A | B; getObjectRef?: undefined };
+>objectRef : Symbol(objectRef, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 9, 6))
+>A : Symbol(A, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 0, 0))
+>B : Symbol(B, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 4, 14))
+>getObjectRef : Symbol(getObjectRef, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 9, 24))
+
+opts.objectRef || opts.getObjectRef();
+>opts.objectRef : Symbol(objectRef, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 8, 6), Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 9, 6))
+>opts : Symbol(opts, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 7, 11))
+>objectRef : Symbol(objectRef, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 8, 6), Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 9, 6))
+>opts.getObjectRef : Symbol(getObjectRef, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 8, 29), Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 9, 24))
+>opts : Symbol(opts, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 7, 11))
+>getObjectRef : Symbol(getObjectRef, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 8, 29), Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 9, 24))
+
+// repro #49643 issuecomment-1174455723
+
+interface X {
+>X : Symbol(X, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 11, 38))
+
+    foo: string;
+>foo : Symbol(X.foo, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 15, 13))
+}
+
+interface Y {
+>Y : Symbol(Y, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 17, 1))
+
+    baz: number;
+>baz : Symbol(Y.baz, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 19, 13))
+}
+
+interface A2 {
+>A2 : Symbol(A2, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 21, 1))
+
+    result: unknown;
+>result : Symbol(A2.result, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 23, 14))
+
+    error: undefined;
+>error : Symbol(A2.error, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 24, 20))
+}
+
+interface B2 {
+>B2 : Symbol(B2, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 26, 1))
+
+    error: X | Y;
+>error : Symbol(B2.error, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 28, 14))
+>X : Symbol(X, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 11, 38))
+>Y : Symbol(Y, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 17, 1))
+}
+
+const testMethod = (m: A2 | B2) => {
+>testMethod : Symbol(testMethod, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 32, 5))
+>m : Symbol(m, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 32, 20))
+>A2 : Symbol(A2, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 21, 1))
+>B2 : Symbol(B2, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 26, 1))
+
+    if (m.error) {
+>m.error : Symbol(error, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 24, 20), Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 28, 14))
+>m : Symbol(m, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 32, 20))
+>error : Symbol(error, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 24, 20), Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 28, 14))
+
+        m; // should be A2 | B2
+>m : Symbol(m, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 32, 20))
+
+    } else {
+        m; // should be A2 | B2
+>m : Symbol(m, Decl(discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts, 32, 20))
+    }
+}
+
+
diff --git a/tests/baselines/reference/discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.types b/tests/baselines/reference/discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.types
new file mode 100644
index 0000000000000..20e677643efa3
--- /dev/null
+++ b/tests/baselines/reference/discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.types
@@ -0,0 +1,74 @@
+=== tests/cases/compiler/discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts ===
+// strictNullChecks: false
+
+// repro #49643
+
+interface A {}
+interface B {}
+
+declare let opts:
+>opts : { objectRef?: undefined; getObjectRef: () => any; } | { objectRef: A | B; getObjectRef?: undefined; }
+
+   | { objectRef?: undefined; getObjectRef: () => any }
+>objectRef : undefined
+>getObjectRef : () => any
+
+   | { objectRef: A | B; getObjectRef?: undefined };
+>objectRef : A | B
+>getObjectRef : undefined
+
+opts.objectRef || opts.getObjectRef();
+>opts.objectRef || opts.getObjectRef() : any
+>opts.objectRef : A | B
+>opts : { objectRef?: undefined; getObjectRef: () => any; } | { objectRef: A | B; getObjectRef?: undefined; }
+>objectRef : A | B
+>opts.getObjectRef() : any
+>opts.getObjectRef : () => any
+>opts : { objectRef?: undefined; getObjectRef: () => any; } | { objectRef: A | B; getObjectRef?: undefined; }
+>getObjectRef : () => any
+
+// repro #49643 issuecomment-1174455723
+
+interface X {
+    foo: string;
+>foo : string
+}
+
+interface Y {
+    baz: number;
+>baz : number
+}
+
+interface A2 {
+    result: unknown;
+>result : unknown
+
+    error: undefined;
+>error : undefined
+}
+
+interface B2 {
+    error: X | Y;
+>error : X | Y
+}
+
+const testMethod = (m: A2 | B2) => {
+>testMethod : (m: A2 | B2) => void
+>(m: A2 | B2) => {    if (m.error) {        m; // should be A2 | B2    } else {        m; // should be A2 | B2    }} : (m: A2 | B2) => void
+>m : A2 | B2
+
+    if (m.error) {
+>m.error : X | Y
+>m : A2 | B2
+>error : X | Y
+
+        m; // should be A2 | B2
+>m : A2 | B2
+
+    } else {
+        m; // should be A2 | B2
+>m : A2 | B2
+    }
+}
+
+
diff --git a/tests/cases/compiler/discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts b/tests/cases/compiler/discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts
new file mode 100644
index 0000000000000..054ba9c683a83
--- /dev/null
+++ b/tests/cases/compiler/discriminatingUnionWithUnionPropertyAgainstUndefinedWithoutStrictNullChecks.ts
@@ -0,0 +1,41 @@
+// @noEmit: true
+// strictNullChecks: false
+
+// repro #49643
+
+interface A {}
+interface B {}
+
+declare let opts:
+   | { objectRef?: undefined; getObjectRef: () => any }
+   | { objectRef: A | B; getObjectRef?: undefined };
+
+opts.objectRef || opts.getObjectRef();
+
+// repro #49643 issuecomment-1174455723
+
+interface X {
+    foo: string;
+}
+
+interface Y {
+    baz: number;
+}
+
+interface A2 {
+    result: unknown;
+    error: undefined;
+}
+
+interface B2 {
+    error: X | Y;
+}
+
+const testMethod = (m: A2 | B2) => {
+    if (m.error) {
+        m; // should be A2 | B2
+    } else {
+        m; // should be A2 | B2
+    }
+}
+