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US vibriosis rates have increased since 1996, and many Vibrio vulnificus infections are fatal. In April 2003, California implemented a regulation restricting the sale of raw oysters harvested from the Gulf of Mexico during April 1-October 31, unless they were processed to reduce V. vulnificus to nondetectable levels. We analyzed California cases of V. vulnificus infection before and after the regulation's implementation and compared case data with data from other states. The annual number of reported V. vulnificus infections and deaths in California with patient's sole exposure to raw oysters dropped from 0 to 6 cases and 0 to 5 deaths per year during 1991-2002, before implementation, to 0 during 2003-2010, after implementation (p = 0.0005 for both). In other states, median annual numbers of similar cases and deaths increased slightly after 2002. The data strongly suggest that the 2003 regulation led to a significant reduction in reported raw oyster-associated V. vulnificus illnesses and deaths. [ABSTRACT FROM AUTHOR]