The frequency of Vibrio vulnificus infection is very rare and there are many questions regarding its epidemiology in Japan. To investigate the clinical course and epidemiology of V. vulnificus infection in Japan, we performed a retrospective questionnaire survey in which 1693 hospitals from all over Japan were surveyed, including advanced life saving emergency centers and dermatology institutions. Of the 1693 hospitals, we received answers from 1045. Ninety-four cases were confirmed as V. vulnificus infections during 1999 and 2003. Sixty-eight (72.3%) of the 94 patients had the septic type infection with a mortality rate of 75.0% (51/68 patients died). The prognosis of patients with the septic type was worse than that of the wound type (P < 0.001). V. vulnificus infections occurred from June to November and none occurred in winter. Many infections occurred in western Japan with the majority of infections (50/94) occurring in Kyushu. In particular, 43 infections occurred in marine coastal areas of the Ariake and Yatsushiro Seas, which have many tidelands. Seventy-seven of 89 patients (86.5%) had liver function impairment as an underlying disease, and 53 (59.6%) had liver cirrhosis, of whom nine (10.1%) suffered from liver cancer. The incidence of V. vulnificus infection was different according to districts. Geographic and climatic factors also contributed to the occurrence of V. vulnificus infection.