In this work we investigated which mitral valve leaflet was most often involved in mitral valve prolapse with degenerative mitral valve disease and whether there was an association with breed, age, gender, or weight. Five hundred and thirty-seven dogs with mitral valve prolapse-degenerative mitral valve disease were assessed; the cross-breed dog was the most represented breed (248 dogs, 46.2%). Mitral valve prolapse was more common in male dogs, and the average age was 11.3 +/- 2.8 years. Prolapse of the anterior leaflet was present in 48.4% of dogs, prolapse of the the posterior leaflet in 7.1%, and bileaflet prolapse was present in 44.5%; this distribution is different than that typically found in humans. There was a significant correlation between severity of mitral regurgitation and severity of mitral valve prolapse or ISACHC class, and between severity of mitral valve prolapse and ISACHC class. There was no relationship between the particular affected leaflet(s) and severity of mitral regurgitation, severity of mitral valve prolapse, or ISACHC class. Our findings suggest that the susceptibility to the mitral valve prolapse-degenerative mitral valve disease is not confined to a specific breeds and that the specific leaflet prolapsing is different in dogs compared with humans.