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Objective: A randomized controlled trial was undertaken to investigate the effect of prophylactic negative pressure dressings on postoperative surgical site infection (SSI) rates in closed laparotomy wounds., Summary of Background Data: Laparotomy wounds are associated with high rates of SSI. The effect of prophylactic negative pressure dressing of closed incisional wounds on SSI rate is unknown., Methods: A randomized, controlled, open-label trial was conducted (clinicaltrials.gov registration number NCT02780453). Fifty patients undergoing open abdominal surgery were included, with 25 patients randomized to the negative pressure dressing group and 25 to the standard dressing group. The primary endpoint was SSI incidence at 30 days postoperatively. Secondary endpoints included SSI incidence at 4 days, length of stay, cosmetic outcome, and patient satisfaction. Statistical analysis was performed on a per-protocol basis using SPSS version 23.0., Results: The incidence of SSI at 30 days postoperatively was significantly reduced in the treatment group compared with the control group [8.3% vs 32.0%, P = 0.043 (1-sided), P = 0.074 (2-sided)]. There was no difference in SSIs at 4 days postoperatively [4.1% vs 8.0%, P = 0.516 (1-sided), P = 1.0 (2-sided)]. Analysis of predictors of wound infection identified standard wound dressings as the only significant predictor of SSI development. Length of stay was significantly reduced in the negative pressure dressing group [6.1 vs 14.7 days, P = 0.019 (2-sided)]. Cosmetic outcome and patient satisfaction did not show any difference between the 2 groups., Conclusions: Prophylactic use of negative pressure dressings for closed laparotomy wounds significantly reduces the incidence of SSI at 30 days postoperatively.