De Mesa wed actress Gina Alajar in 1978. Their marriage lasted 23 years before they separated in 2001. Their marriage was annulled in 2006, but bore three children, all of whom are in show business: Ryan, Geoff, and AJ Eigenmann. He married Julie Reyes in September 2011. She is a dancer/choreographer from Hotlegs, Manila's premier jazz group.