Purpose: The presentation describes a case of a five-finger replant, complicated by clostridium difficile colitis requiring total colectomy following leech therapy with antibiotic prophylaxis. It presents a literature review of antibiotic prophylaxis in hirudotherapy and discusses risks and complications. Background: A teenage boy suffered traumatic five-digit amputation. An 18-hour operation was performed resulting in successful five-digit replantation. Day three post-operatively venous compromise was noted, and leech therapy initiated with Bactrim as antibiotic prophylaxis. Within 48 hours the patient deteriorated secondary to severe clostridium difficile colitis. After failure of medical therapy, total colectomy with ileostomy was performed. Hirudotherapy is utilised within plastic and reconstructive surgery for venous compromise in flaps or digital replants. It may be complicated by aeromonas infections in 2.4-36% of cases, and subsequently most authors advocate for antibiotics prior to therapy until 24 hours after. A four-year review of leech therapy found an infection rate of 20%, and a statistically significant association between antibiotic prophylaxis and reduced incidence of infection (26% vs 13%). Despite this, a UK study found 24% of units didn’t use prophylaxis, and 57% used potentially ineffective agents, oft citing risks of antibiotic therapy. Conclusions: Within the literature, numerous articles describe benefit of prophylactic antibiotic therapy in hirudotherapy. In all surgical patients, treatment with antibiotics can be associated with severe complications and should be reserved for evidence-based indications.