We report two cases of Vibrio vulnificus wound infection leading to fulminant sepsis syndrome in immunocompromised solid organ transplant recipients. Features of clinical presentation in each of these cases suggest that host immune factors are of great importance in the virulence of this organism and that immunocompromised recipients of solid organ transplants are particularly vulnerable to life-threatening consequences from infection with Vibrio vulnificus. Prompt institution of antibiotic therapy and early consideration for surgical wound debridement are the mainstay of successful management. Heart and other organ transplant recipients should be educated and warned about the hazards associated with raw oysters and shellfish consumption and asked to exercise caution when exposed to a salt water environment.