We analyzed data from pathologic investigations in the United States, collected by the USGS National Wildlife Health Center between 1971 and 2005, into aquatic bird mortality events. A total of 3619 mortality events was documented for aquatic birds, involving at least 633 708 dead birds from 158 species belonging to 23 families. Environmental causes accounted for the largest proportion of mortality events (1737 or 48%) and dead birds (437 258 or 69%); these numbers increased between 1971 and 2000, with biotoxin mortalities due to botulinum intoxication (Types C and E) being the leading cause of death. Infectious diseases were the second leading cause of mortality events (20%) and dead birds (20%), with both viral diseases, including duck plague (Herpes virus), paramyxovirus of cormorants (Paramyxovirus PMV1) and West Nile virus (Flavivirus), and bacterial diseases, including avian cholera (Pasteurella multocida), chlamydiosis (Chalmydia psittici), and salmonellosis (Salmonella sp.), contributing. Pelagic, coastal marine birds and species that use marine and freshwater habitats were impacted most frequently by environmental causes of death, with biotoxin exposure, primarily botulinum toxin, resulting in mortalities of both coastal and freshwater species. Pelagic birds were impacted most severely by emaciation and starvation, which may reflect increased anthropogenic pressure on the marine habitat from over-fishing, pollution, and other factors. Our study provides important information on broad trends in aquatic bird mortality and highlights how long-term wildlife disease studies can be used to identify anthropogenic threats to wildlife conservation and ecosystem health. In particular, mortality data for the past 30 yr suggest that biotoxins, viral, and bacterial diseases could have impacted >5 million aquatic birds.