BACKGROUND: Prevention of surgical site infections (SSIs) can improve surgical quality through reductions in morbidity and cost. We sought to determine whether the abdominal closure protocol, in isolation, decreases SSI at an academic teaching hospital. METHODS: Adult patients undergoing laparotomy were prospectively randomized to an abdominal closure protocol, which includes unused sterile instruments and equipment at fascial closure, or usual care. A 30-day SSI rates were compared. General surgery, colorectal, urology, or gynecologic oncology patients undergoing anticipated wound classification II cases were eligible. RESULTS: Overall SSI rates were 11.6% in patients randomized to protocol closure vs 12.4% for usual care (total n = 233; P = .85). The abdominal closure protocol and usual care groups had similar rates of superficial (4.5% vs 4.1%; P = .9), deep (.9% vs 0%, P = .3), organ-space SSI rates (6.2% vs 8.3%, P = .55), and wound dehiscence (2.7% vs 5.3%; P = .24). CONCLUSIONS: An abdominal closure protocol did not decrease the rate of SSI and is likely not a key intervention for SSI reduction.