diff --git a/src/changelog/unreleased.md b/src/changelog/unreleased.md
index 2b04d1a69d..c0d43fd3ec 100644
--- a/src/changelog/unreleased.md
+++ b/src/changelog/unreleased.md
@@ -158,6 +158,8 @@ changelog entry.
   - In the same spirit rename `DeviceEvent::MouseMotion` to `PointerMotion`.
   - Remove `Force::Calibrated::altitude_angle`.
   - On X11, use bottom-right corner for IME hotspot in `Window::set_ime_cursor_area`.
+- Main thread check is now more lax on Windows due to it not being fully reliable: it now produces a log instead
+  of a hard panic, and is not checked without `cfg(debug_assertions)`.
 
 ### Removed
 
diff --git a/src/event_loop.rs b/src/event_loop.rs
index 059613459b..09dffbeaa4 100644
--- a/src/event_loop.rs
+++ b/src/event_loop.rs
@@ -71,7 +71,7 @@ impl EventLoopBuilder {
     ///
     /// ## Panics
     ///
-    /// Attempting to create the event loop off the main thread will panic. This
+    /// Attempting to create the event loop off the main thread may log or panic. This
     /// restriction isn't strictly necessary on all platforms, but is imposed to
     /// eliminate any nasty surprises when porting to platforms that require it.
     /// `EventLoopBuilderExt::with_any_thread` functions are exposed in the relevant
diff --git a/src/platform_impl/windows/event_loop.rs b/src/platform_impl/windows/event_loop.rs
index 874ae06a8c..674bb8bb4e 100644
--- a/src/platform_impl/windows/event_loop.rs
+++ b/src/platform_impl/windows/event_loop.rs
@@ -186,13 +186,22 @@ impl EventLoop {
     ) -> Result<Self, EventLoopError> {
         let thread_id = unsafe { GetCurrentThreadId() };
 
+        #[cfg(debug_assertions)]
         if !attributes.any_thread && thread_id != main_thread_id() {
-            panic!(
-                "Initializing the event loop outside of the main thread is a significant \
-                 cross-platform compatibility hazard. If you absolutely need to create an \
-                 EventLoop on a different thread, you can use the \
-                 `EventLoopBuilderExtWindows::with_any_thread` function."
-            );
+            const MESSAGE: &str = "Initializing the event loop outside of the main thread is a \
+                                   significant cross-platform compatibility hazard. If you \
+                                   absolutely need to create an EventLoop on a different thread, \
+                                   you can use the `EventLoopBuilderExtWindows::with_any_thread` \
+                                   function.";
+
+            // If we're not the main module, it's possible for main_thread_id() to be incorrect.
+            // See https://github.com/rust-windowing/winit/issues/3999
+            // In that case, log a warning instead of an outright panic.
+            if is_self_main_module() {
+                panic!("{}", MESSAGE);
+            } else {
+                tracing::warn!("{}", MESSAGE);
+            }
         }
 
         if attributes.dpi_aware {
@@ -556,10 +565,12 @@ impl rwh_06::HasDisplayHandle for OwnedDisplayHandle {
 /// to setup global state within a program. The OS will call a list of function pointers which
 /// assign values to a static variable. To have get a hold of the main thread id, we need to place
 /// our function pointer inside of the `.CRT$XCU` section so it is called before the main
-/// entrypoint.
+/// entrypoint. Note that when compiled into a dylib, this is not guaranteed to be ran from the
+/// "main" thread, so this is not foolproof.
 ///
 /// Full details of CRT initialization can be found here:
 /// <https://docs.microsoft.com/en-us/cpp/c-runtime-library/crt-initialization?view=msvc-160>
+#[cfg(debug_assertions)]
 fn main_thread_id() -> u32 {
     static mut MAIN_THREAD_ID: u32 = 0;
 
@@ -583,6 +594,31 @@ fn main_thread_id() -> u32 {
     unsafe { MAIN_THREAD_ID }
 }
 
+/// Check if winit is compiled into the main module (.exe).
+#[cfg(debug_assertions)]
+fn is_self_main_module() -> bool {
+    use std::ptr::null;
+
+    use windows_sys::Win32::Foundation::HMODULE;
+    use windows_sys::Win32::System::LibraryLoader::{
+        GetModuleHandleA, GetModuleHandleExA, GET_MODULE_HANDLE_EX_FLAG_FROM_ADDRESS,
+        GET_MODULE_HANDLE_EX_FLAG_UNCHANGED_REFCOUNT,
+    };
+
+    unsafe {
+        let mut winit_module: HMODULE = 0;
+        GetModuleHandleExA(
+            GET_MODULE_HANDLE_EX_FLAG_FROM_ADDRESS | GET_MODULE_HANDLE_EX_FLAG_UNCHANGED_REFCOUNT,
+            is_self_main_module as *const u8,
+            &mut winit_module,
+        );
+
+        let main_module = GetModuleHandleA(null());
+
+        winit_module == main_module
+    }
+}
+
 /// Returns the minimum `Option<Duration>`, taking into account that `None`
 /// equates to an infinite timeout, not a zero timeout (so can't just use
 /// `Option::min`)