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Purpose. To evaluate the results of Damage Control Strategy (DCS) in the treatment of generalized peritonitis from perforated diverticular disease in patients with preoperative severe systemic diseases. Methods. All the patients with diffuse peritonitis (Hinchey 3 and 4) and the American Society of Anesthesiologists (ASA) score ≥3 were included and underwent DCS consisting of a 2-step procedure. The first was peritoneal lavage, perforated colon-stapled resection, and temporary abdominal closure with negative pressure wound therapy combined with instillation. The second step, 48 hours later, included the possibility of restoring intestinal continuity basing on local and general patients’ conditions. Results. Thirty patients (18 [60%] women and 12 [40%] men, median age 68.5 [range = 35-84] years) were included (18 [60%] ASA III, 11 [36.7%] ASA IV, and 1 [0.03%] ASA V). Seven patients (23.3%) showed sepsis and 1 (3.33%) septic shock. At second surgery, 24 patients (80%) received a colorectal anastomosis and 6 patients (20%) underwent a Hartmann’s procedure. Median hospital stay was 18 days (range = 12-62). Postoperative morbidity rate was 23.3% (7/30) and included 1 anastomotic leak treated with Hartmann’s procedure. Consequently, at discharge from hospital, 23 patients (76.6%) were free of stoma. Primary fascial closure was possible in all patients. Conclusions. DCS with temporary abdominal closure by negative pressure wound therapy combined with instillation in patients with diffuse peritonitis from complicated diverticulitis could represent a feasible surgical option both in hemodynamically stable and no stable patients, showing encouraging results including a low stoma rate and an acceptable morbidity rate.