If DDR3 and in particular with DRAM 1600 and above, ANY time you mix sticks it can be problematic, even if they are the same exact model. When you buy a packaged set they have been tested to work together and if 1600 and up are programmed with XMP, even with the same model of sticks, that XMP programming will differ in the advanced timings, particularly the tRFC timing as it requires a higher number than does a lower count set, I.E> 2x8GB set may require 208 where the same model 4x8GB may take 314. Also differences in the PCB used, the ICs used, etc may be different, or they may be from different production lots. If you are comfortable with playing in the advanced timings (most people aren't) and voltages (DRAM and MC) then chances are good, if they don't play you are looking at an RMA. This mixing of sticks is usually the bigggest reason for RMA's and generally of sticks sticks returned as BAD from people doing this about 80% or more are perfectly fine....This used to be a perfectly accepted practive with the old DDR and DDR2, but DDR3 has much finer tolerances. If you have sticks, that are similar, by all means give them a shot - I know I can often help people get them to work but when you hit 1866 and above it's even harder....I help people try basically daily through the GSkill forums. So if buying new, best practice is buying a single set of the full amount you want....If it was as easy as people say all to often, then the DRAM makers wouldn't waste all the time testing and setting up packaged sets, they'd make more money just selling single stick packages - problem there, people seldom ever use a single stick and RMAs would skyrockets by thousands of percents