Background: The aim of this randomized clinical trial was to determine whether a single intravenous dose of 2 g flucloxacillin could prevent wound infection after primary non-reconstructive breast surgery.Methods: The study included 618 patients undergoing local excision (77 = 490), mastectomy (n = 107) or microdochectomy (n = 21). Patients were randomized to receive either a single dose of flucloxacillin immediately after the induction of anaesthesia or no intervention. Wound morbidity was monitored by an independent research nurse for 42 days after surgery.Results: The incidence of wound infection was similar in the two groups: 10 of 311 (3.2 per cent) in the flucloxacillin group and 14 of 307 (4.6 per cent) in the control group (chi(2) = 0.75, P = 0.387; relative risk 0.71, 95 per cent confidence interval 0.32 to 1.53). The groups also had similar wound scores and rates of moderate or severe cellulitis. Wound infection presented a median of 16 days after surgery.Conclusion: The administration of a single dose of flucloxacillin failed to reduce the rate of wound infection after non-reconstructive breast surgery.