If a bounce solves it, the disk I/O buffers (for samples) may be part of the issue as well as effects being used on some tracks. Does bypassing effects (E hotkey) also solve the issue?

He reported trying the effects bypass earlier, in post #4, without success.
 
Bob Bone
 

Mathew, I think you should be increasing your ASIO buffers, not lowering them. Focusrite uses the Dice II chipset for their Firewire interfaces. It's one reason Focusrite products are so reasonably priced, but they are notorious for having poor low-latency performance. I'm a Focusrite user, too, but mine's permanently set at 2048 samples (obviously, I don't care about low latency) and never experience the kinds of issues you're describing.
 
EDIT: I just realized your interface is USB, so disregard the DICE II comment above.

I'm 99% sure that I had all samples loaded in memory.  I will also check is just deleting the instruments and reloading them works.

Are you having these issues while recording, or while just playing back?
 
If recording, the ASIO Buffer Size should be pretty small, but for playback, particularly with effects, you want to jack up the ASIO Buffer Size quite a bit, since latency during mixing isn't really an issue. On my interface UI, ASIO Buffer is controlled with a parameter called ASIO Buffer Size,  and when mixing, I raise my ASIO Buffer Size from 128 (when I record), up to 1024 (mixing). 
 
Also, in Edit>Preferences>MIDI>Playback and Recording, you could try increasing your Prepare Using nnn Millisecond Buffers from the default of 250 up to 500.  That might help.  
 
Bob Bone
 
 
 

I get it on both.  Note I switch between record and playback modes ALL the time. so I usually just find a latency that works for me, and stick with it.  I don't have the best hands, so something in the 10-20ms range is usually fine for me.    I usually quantize anyway

Uh - and what happens if you increase the Prepare Using.... as posted above?
 
Bob Bone

I think it was already mentioned but there was no response. I had the same problem with another audio interface. Turned out to be this terrible EIST that puts your machine in a too low CPU speed not understanding it has to boost performance. You should absolutely make sure you have it disabled in your BIOS. I turned off EIST and the related monitoring options, if your motherboard has them (or else it won't work). Never had a problem like this again.
 
Hope it helps.....
Best regards,
 
Rinie

I will check into the speedstep as well, sorry I forgot about that.

Mathew, I'm a big Play user.  Your system is 10 times more powerful than mine… I never have problems with Play. I'm a "light" user, but i have templates with 10 instances of Play with master key switch instruments in each and only 8gigs of ram.  I never come close to stressing my system.  However, there are some settings in Play that can affect performance if you change from the defaults… You might try the Soundsonline forum for info about specific settings…and you should make sure your Play is up to date.
 
That being said, I have, in the long past, had an issue with transferring or opening an old project with instances of Play (after upgrading to a newer Sonar version or a newer version of Play) where one of my Play instances did, indeed, become corrupted.  Traced it down by freezing/unloading each instance until I found the offending instance.  Then it was just a matter of deleting the offending instance and reloading another instance and re=connecting the ins/outs of the midi tracks.
 
In your first post, you mention "multitasking".  Are you connected to the Internet while working?  Are you connected wirelessly?  Any antivirus programs running?  All three of these things can randomly affect your performance, I believe...
 
Best,
Rob