RoadHazard386: Update: Fixed it!
Tweaking the .ini files didn't work for me but downloading the mod below did. I ignored the advice from other threads that recommended this mod because I don't have Intel graphics or Nvidia graphics, so I figured the mod didn't apply to me. Nevertheless, it fixed the crashes.
www.nexusmods.com/fallout3/mods/17209
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Resurrecting this old thread...
Just bought & installed this game on my Windows 10 Pro with Ryzen 9 + Radeon RX 6600 XT and it crashes to desktop right after selecting "New Game."
I've tried different graphic options, like window vs. full-screen and different resolutions, but no joy. I do get a Windows pop-up every time I launch the game warning me that "This app may not work correctly... because it causes security or performance issues on Windows."
Any updated hints, tips, or tricks?
I have the same problem.