There are two parts. The first having to do with a pesky INI file, and the latter with setting the mode for the executable.
Open up the fallout.ini file in: My Documents\My Games\Fallout3
This limits the game to utilizing 2 cores and supposedly this stabilizes some instabilities, preventing the engine from wreaking memory havoc ending in game freezes and crashes.
Right-click on the Executable and set the Compatibility mode to Windows XP (SP3)
Likewise, set the executable to run in Administrator mode
That should do it. Obviously have the latest DirectX, drivers, blah blah blah. Now go kill some damned ghouls!