That's usually a sign that something in your audio chain isn't running at exactly the same clock as the rest.
Have you checked Preferences->Device in Reaper?
There is a checkbox "Request sample rate" and "Request block size". For some interfaces these need to be checked. Try checking "Request sample rate", of course with the correct value for your project's sample rate.
Normally, Core Audio will resample "automagically" and sometimes that turns out less than ideal.
Also, check "Audio/midi setup" and confirm all settings. Sometimes it looks OK, but it isn't.
[EDIT]
And it's always a good idea to split long recordings...
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