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We report a case of ceftriaxone-resistant Aeromonas hydrophila infection in a 32-year-old man after medicinal leech therapy. The patient underwent a free gracilis muscle flap for dorsal foot soft tissue reconstruction. Because of persistent congestion after venous revision, medicinal leech therapy was initiated to aid in flap salvage. Intravenous ceftriaxone was administered prior to application of leeches for prophylaxis against A. hydrophila. Leech therapy was discontinued after 1 week, and ceftriaxone was discontinued 24 hours thereafter. An infection developed despite being on appropriate antibiotics. Culture sensitivities indicated that A. hydrophila was resistant to ceftriaxone.