Twenty patients undergoing upper extremity reconstructive surgery were randomized to receive either regional IV perfusion of vancomycin (125 mg in 50 ml saline) (n=10) or systemic IV vancomycin (1 g) (n=10). The primary outcome of interest was the difference in vancomycin concentration in bone and fat tissue between the groups. Secondary outcomes of interest included tissue concentrations at various time points and complications related to drug delivery. Outcomes were assessed at 5–10 minutes, 20–25 minutes after skin incision, and at wound closure. Overall, the results of the study revealed that tissue concentrations of vancomycin were significantly higher in the regional IV perfusion group across all time points, with no observed complications in either group. These findings suggest Bier block administration may offer a safer and more effective alternative to systemic prophylaxis in upper extremity surgery.