I recently blogged about installing a 64-bit build of Emacs for Windows because I was dealing with a bunch of large and very large files.
While the 64-bit build definitely handled the really large files much better than the 32-bit build, there were still some performance issues. The main advantage of using the 64 bit build was that I could finally load a couple of files that I wasn't able to load on the 32-bit build, but opening the files severely tested my patience.
The other problem that I didn't think about initially was that if you happen to have
desktop-save-mode turned on, Emacs will of course reload the large files every time you restart it, unless you remember to close large files before shutting down Emacs. That tends to take a considerable amount of time because either build of Emacs is rather slow when it comes loading files in the hundreds of megabytes or bigger category.
A commented in the previous post kindly suggested to use VLF for large files, which is what I've been doing instead. I keep forgetting to turn on the integration which should save me from having to remember to manually kick off vlf every time I want to open a large file, but other than that it just works.
Highly recommended if you need to deal with large files from time to time.