© Wolters Kluwer Health, Inc. All rights reserved.OBJECTIVE To determine the effect of prophylactic negative-pressure wound therapy (pNPWT) in patients at high risk of surgical wound complications (SWCs) who underwent colorectal cancer (CRC) surgery. METHODS In an open-label randomized controlled trial, 50 patients who underwent open CRC surgery between November 2018 and February 2020 were included. Participants were randomly assigned to the pNPWT group (n = 24) or control group (n = 26). For patients in the pNPWT group, the pNPWT device was placed on the wound for 7 days, whereas for patients in the control group, the wound was covered with a sterile gauze dressing. The primary outcome measured was 30-day SWCs: surgical site infection, hematoma, seroma, and wound dehiscence/evisceration. Secondary outcomes included postoperative wound infection assessment score and length of postoperative hospital stay. RESULTS The incidence of 30-day SWCs differed significantly between the pNPWT and control groups (16.7% vs 53.8% respectively, P =.006). Patients in the pNPWT group had a significantly lower incidence of seroma than did those in the control group (8.3% vs 34.6%, P =.025). Surgical site infection occurred in 10 of 50 patients (20%) in the study: Two (8.3%) in the pNPWT group and eight (30.8%) in the control group (P =.048). No hematomas or wound dehiscence/evisceration were noted in the study. There was no difference in median length of stay between groups (P =.153). CONCLUSIONS This study confirmed that pNPWT effectively helps prevent SWCs in high-risk wounds after open CRC surgery.