The same thing happened to me when I had to take Cleo to the vet to have a small cut taken care of. My cats are close to three years old too, they are litter mates, and have been to the vet separately before. Both are fixed. When I brought Cleo home from the vet, Alex (my male cat) was hissing and growling and I had no idea what was going on. We called the vet and they explained to us how much cats rely on scent to recognize eachother. We kept them separated for a bit so they could smell eachother under the door, we also transfered their scents with a towel, but Alex didn't take to that very well. After a couple of days I let them out into the same room under my supervision and got them to play with me. They were more interested in chasing the cat toy then hissing at each other. Actually Alex was more of the aggressor, but eventually Cleo got fed up with him and hissed and batted back. Once I got them playing with me, they began to calm down. After a few more days they were back to normal. Recently we moved, and when we finally let the cats out into the bedroom, Alex was hissing and growling at Cleo again. He stopped after a day, but I'm learning that as he has begun to reach adulthood, he is more stressed out by unfamiliar smells and he tells Cleo to back off. I know how awful it is to see your kitties behave that way to each other when they were best of friends, but don't worry they will be back to normal. It may take a week or two, but it will be alright.