Objective: To evaluate the efficacy of incisional negative pressure wound therapy in the prevention of postoperative wound morbidity in women with class III obesity undergoing cesarean delivery. Methods: In an open label randomized controlled trial, women admitted for delivery with class III obesity (body mass index 40 or higher) measured within 2 weeks of admission for delivery were offered participation in the study. They were consented either in the outpatient maternal-fetal medicine specialty clinic, during admission to labor and delivery and before a decision to perform cesarean delivery, or in the preoperative area of the hospital before scheduled cesarean delivery. Exclusion criteria included anticoagulation therapy, human immunodeficiency virus infection, and silver or acrylic allergy. Those who ultimately underwent cesarean delivery were randomized to standard surgical dressing or incisional negative pressure wound therapy dressing. The primary outcome was wound morbidity. Preplanned secondary outcomes included characteristics of composite wound morbidity, and hospital, emergency room, and clinic utilization. The sample size estimate required randomization of 440 women to detect a 50% decrease in composite outcome. Results: Between January 1, 2015, and July 31, 2016, 850 women were screened and 677 women with class III obesity were enrolled. Of these, 441 underwent cesarean delivery and were subsequently randomized (219 to standard dressing and 222 to incisional negative pressure wound therapy). The primary outcome, overall composite wound morbidity rate, was 18%. This was not different between the two cohorts (incisional negative pressure wound therapy 17% vs standard dressing 19%, relative risk 0.9 [95% CI 0.5-1.4]). Conclusion: Prophylactic incisional negative pressure wound therapy use did not reduce postoperative wound morbidity when compared with a standard surgical dressing in women with class III obesity.