I have never used either product. I like the Simperica Trio better because it's a pill and stays in the body a short time. The Advantage Multi is liquid drops, that is supposed to work for a month....but I always wonder about how effective it is if the dog swims, or just does rolls in the wet grass.
Both have side effects, just as most of the flea/tick/heartworm meds do. Do you have a problem with ticks and fleas in your area?? I don't think there is a good, better, best for any of these medications. It depends on what your dog can handle, and how high a chance there is of your dog getting fleas/ticks/heartworm in your area.
My Jemma could not stand any of the drop type of medications...I tried Revolution on her one year. She would roll, flip, drool for hours after I put it on. I stuck with Heartgard Plus for her, and if there was any chance of thinking she may have a flea ( we don't have problems with fleas in my area)...then I used Advantage. Less is always better for my dogs.