Prevention of surgical site infection (SSI) is a public health challenge. The objective of the study was to evaluate the efficacy of negative pressure wound therapy (NPWT) for preventing SSI and other wound complications in obese women undergoing cesarean section. The search terms included “negative pressure wound therapy”, “obesity” and “cesarean section/delivery”. Randomized controlled trials were used to compare the use of NPWT to standard dressings in preventing SSI in obese women after cesarean section. A comprehensive literature search of four databases was performed up to June 2021. The primary outcome was SSI. Secondary outcomes were seroma, hematoma, overall wound complications, and adverse skin reactions. Ten RCTs involving 5586 patients met the inclusion criteria. The use of NPWT reduced SSI (RR = 0.76, 95%CI: 0.63–0.92, P = 0.004). No statistically significant difference was detected in the incidence of overall wound complications (RR = 0.93, P = 0.48), seroma (RR = 1.10, P = 0.79), hematoma (RR = 0.63, P = 0.36) and hospital readmission (RR = 1.41, P = 0.15). NPWT significantly increased the occurrence of skin blistering with a RR of 4.60 (P = 0.04). Use of prophylactic NPWT after cesarean delivery among obese women is associated with a significant reduction of surgical site infection.