Endemic disease transmission is an important ecological process that is challenging to study because of low occurrence rates. Here, we investigate the ecological drivers of two coral diseases-growth anomalies and tissue loss-affecting five coral species. We first show that a statistical framework called the case-control study design, commonly used in epidemiology but rarely applied to ecology, provided high predictive accuracy (67-82%) and disease detection rates (60-83%) compared with a traditional statistical approach that yielded high accuracy (98-100%) but low disease detection rates (0-17%). Using this framework, we found evidence that 1) larger corals have higher disease risk; 2) shallow reefs with low herbivorous fish abundance, limited water motion, and located adjacent to watersheds with high fertilizer and pesticide runoff promote low levels of growth anomalies, a chronic coral disease; and 3) wave exposure, stream exposure, depth, and low thermal stress are associated with tissue loss disease risk during interepidemic periods. Variation in risk factors across host-disease pairs suggests that either different pathogens cause the same gross lesions in different species or that the same disease may arise in different species under different ecological conditions.