It is hard to pick exactly, not to mention if you mean as a writer or director or both.

It is hard for me to go against National Lampoon's Christmas Vacation as it is my families go to Christmas film and I still love it.

After that he was involved in another of my favorite comedies in Planes, Trains and Automobiles. But to be fair, the guy was involved in some of the best John Candy movies out there (Spaceballs and a few others non-withstanding).