The purpose of this retrospective study was to evaluate diaphragmatic surgery in achieving optimal cytoreductive results and its associated complications during interval debulking surgery in patients with advanced ovarian cancer. After retrospective review of medical records, diaphragmatic surgery was performed in 74 of 128 consecutive patients with advanced epithelial ovarian cancer who underwent interval debulking, between September 1993 and December 2007. Four different approaches were performed: coagulation (group 1), stripping (group 2), combination of stripping with coagulation (group 3), and diaphragm full-thickness resection including muscle with pleura (group 4). Cytoreductive outcome, morbidity, overall survival, and disease-free survival were analyzed. Two patients (2.7%) had International Federation of Gynecology and Obstetrics stage IIIB disease; 46 (62.16%), stage IIIC; and 26 (35.13%), stage IV. After 3 to 4 cycles of neoadjuvant platinum-based chemotherapy, the diaphragmatic disease was coagulated in 43 patients (58.10%) and was only stripped in 10 (13.51%); in 19 patients (25.67%), a combination of these techniques was applied; and in 2 (2.70%), the disease was resected, with the adjacent infiltrated part of the diaphragmatic muscle and the pleura above it. Debulking to no residual was achieved in 95%, 100%, 100%, and 50% for groups 1, 2, 3, and 4, respectively. The median disease-free survival was 15, 14, and 14 months, and the median overall survival was 34, 30, and 51 months for groups 1, 2, and 3, respectively, and were not reached for group 4. Minor and major complications were comparable among the groups. Pleural effusions were the most frequent associated complication, and chest tube placement (1.3%) or thoracocentesis (4%) were necessary for the relief of respiratory distress. The perioperative mortality rate was 0%. Diaphragmatic surgery during interval debulking enhances optimal cytoreduction rates and improves survival with acceptable and manageable morbidity. In patients with thick (>4 mm) or large (>1 cm) lesions, stripping the diaphragm or full-thickness resection of the diaphragmatic muscle is preferred.