In this study we describe a technique for the delivery of regional antibiotic prophylaxis in patients undergoing elbow surgery and compare tissue antibiotic concentrations achieved by this technique with those achieved by standard systemic intravenous prophylaxis. We collected bone and fat samples from patients undergoing elective elbow surgery who had received regional antibiotic prophylaxis and measured the tissue antibiotic concentration. For comparison, we measured the antibiotic concentration in bone and fat samples taken from patients undergoing elective shoulder surgery who had received systemic prophylaxis. Mean tissue antibiotic concentrations were significantly higher in the regional antibiotic group (bone, 1484 microg/g vs 35.8 microg/g; fat, 1422.7 microg/g vs 10.7 microg/g; P <.05). No adverse effects were encountered with regional antibiotic delivery. The delivery of regional antibiotic prophylaxis in elbow surgery achieves higher tissue antibiotic concentrations than those achieved with standard systemic delivery. This technique may help reduce the risk of perioperative infection in elbow surgery.