We determined the ferrophilic characteristics of Vibrio vulnificus to evaluate the potential usefulness of iron chelation therapy for the prevention of V. vulnificus infection. Readily available non-transferrin-bound iron (NTBI) is required for the initiation of V. vulnificus growth under in vitro iron-limited conditions and human ex vivo conditions. NTBI aided efficient transferrin-bound iron (TBI) use by V. vulnificus, and the vulnibactin-mediated iron-uptake system was expressed after bacterial growth had been started by NTBI. V. vulnificus required higher NTBI levels for the initiation of growth, produced siderophores at lower levels, and used TBI less efficiently than other bacteria. In addition, the growth of V. vulnificus was inhibited by deferiprone, a clinically available iron chelator. These results show that V. vulnificus is a ferrophilic bacterium that requires higher NTBI levels than other pathogens and that iron chelation therapy might be an effective means of preventing the in vivo growth of V. vulnificus in susceptible patients.