Background Surgical-site infections (SSIs) are found to occur after about 2–5% of all surgeries. SSIs have many drawbacks such as the need for readmission, revision operations, prolonged duration of hospital stay, increased financial burden on patients and increased risk of worsening outcome in cancer patients. Closed-incision negativepressure therapy (CINPT) was studied as a method of preventing infections in wounds occurring after closed surgical incisions particularly during the covid-19 pandemic. There are many studies showed promising results of this procedure. Therefore, in this prospective clinical randomized study, we aimed to evaluate the benefit of performing prophylactic CINPT in controlling SSIs in open colorectal surgeries, hepatobiliary surgeries and gynecological cancer surgeries involving laparotomies, in comparison with the standard dressings. Patients and method We included 120 patients of SSIs with open colorectal surgeries, hepatobiliary surgeries and gynecological cancer surgeries involving laparotomies in the period between 2015 and 2020. We divided the patients randomly into two groups: the first group is the study group, which included 30 patients managed by CINPT, and the second group is the control group, which included 90 patients managed by standard non-CINPT management. We compared patients who underwent CINPT with the control group of high-risk patients undergoing routine management non- CINPT procedures. Results The median rate of occurrence of general adversewound outcomeswas 32.5%for all the included patients: 20% in the CINPT group and 36.7% in the control group (P =0.049). The median rate of occurrence of SSIs was 17.5% for all the included patients: 7% in the CINPT group and 15% in the control group (P=0.001). Time to diagnose SSIs in the CINPT group was longer than that in the control group (19 vs 13 days;P=0.03). The increased duration of operation and the presence of preoperative or postoperative stoma were associated with increased incidence of occurrence of SSI, while CINPT was associated with decreased incidence of occurrence of SSIs (P<0.001). Conclusion We observed a marked reduction in the rates of SSIs in closed laparotomy wounds in colorectal, hepato-pancreato-biliary and in gynecological oncology surgeries managed with prophylactic CINPT particularly during the Covid-19 pandemic.