I have had this happen over the last 2 years quite often but not enough to discourage me from Reaper. I LOVE this DAW and will continue to use it! But alot of my projects start to breakdown over a period of time as I'm tweaking them and tightening up trks adding different plugs ect....I even mixdown and save FX to trks to take off any undo workload but still same prob.....It's like something starts building up and gets everything jammed up with these projects at certain points.... THE MAIN ISSSUE: My project sounds great and I still need to do some more work on it. I open it up the next day and it gets to specific points and starts stuttering. If I put all FX offline it is fine but with all FX online the performance meter is still around 89% and not overloaded. I have a dual core pentium with 3 gigs of Ram, Vista os, RME interface any ideas?? I have tried to search this problem and haven't found the solution or maybe I looked in the wrong places??

When mixing, latency is no issue, so you can set your asio buffer some large value. Try that. Then... Vista is known to be obnoxious when it comes to DAWing.

What does your memory use look like? Watch to see if the memory use creeps up steadily while you are working on the project, which would indicate a memory leak somewhere.

I had a similar issue some time back and it turned out to be an auto panner and or a Reverb with a very long tail. Once it appeared the "crackle" would show up in the same place on playback but would not be there on render. See if you can isolate it to a single track by soloing and then see if you can narrow it down to a specific fx. Just a thought.