In cardiac surgery, sternal wound infection (SWI) continues to be one of the most serious postoperative complications. Coagulase-negative staphylococci (CoNS) have become the most common causative agents of SWI. However, many CoNS species are resistant to routine intravenous antibiotic prophylaxis. 2000 cardiac surgery patients were randomised to routine prophylaxis with intravenous isoxazolyl penicillin alone (control group) or to this prophylaxis combined with application of collagen-gentamicin (260 mg gentamicin) sponges within the sternotomy before wound closure. The primary end-point was any sternal wound infection within 2 months postoperatively. The incidence of any sternal wound infection was 4.3% in the treatment group and 9.0% in the control group (relative risk=0.47; 95% confidence interval 0.33 to 0.68; P<0.001). Local gentamicin reduced the incidence of SWI caused by all major clinically important microbiological agents, including CoNS. Routine use of the described prophylaxis in all adult cardiac surgery patients could be recommended.