We examined clinical and epidemiological features of 575 laboratory-confirmed cases of vibrio gastroenteritis in Alabama, Florida, Louisiana, and Texas from 1988 to 1997 (the US Gulf of Mexico Regional Vibrio Surveillance System). Illnesses occurred year round, with peaks in spring and autumn. Illnesses lasted a median of 7 days and included fever in half of patients and bloody stools in 25% of patients with relevant information. Seventy-two percent of patients reported no underlying illnesses. In the week before onset, 236 (53%) of 445 patients for whom data were available ate raw oysters, generally at a restaurant or bar. Educational efforts should address the risk of vibrio gastroenteritis for raw oyster consumers, including healthy individuals. Further studies should examine environmental conditions affecting vibrio counts on seafood and processing technologies to enhance the safety of raw oysters.