Background Laparoscopy has acquired an increasing role in the management of ovarian cancer. Laparoscopic cytoreduction could represent a new frontier for selected patients after neoadjuvant chemotherapy (NACT). Objective We sought to assess feasibility and early complication rate of minimally invasive (MI) interval debulking surgery (IDS) in stage III-IV epithelial ovarian cancer (EOC) patients after NACT. Study Design This is a phase II multicentric study in advanced EOC cases with clinical complete response after NACT, according to Gynecologic Cancer Intergroup and Response Evaluation Criteria In Solid Tumors criteria. Institutional review board approval was obtained and all patients signed written informed consent to be included in the protocol. The study was registered in clinicaltrials.gov (NCT02324595) and was named "MISSION" trial. For patients meeting inclusion criteria, surgical procedures started with diagnostic laparoscopy to confirm preoperative findings and assess surgical complexity. MI-IDS included hysterectomy, bilateral salpingo-oophorectomy, appendectomy, omentectomy, peritonectomy, and bowel resection. Pelvic and/or aortic lymphadenectomy was not considered as standard procedure in these cases. Intraoperative and postoperative outcomes, time to restart chemotherapy, survival rate, and quality of life data were registered. Results From December 2013 through February 2015, of 184 advanced EOC patients considered eligible for IDS, 52 (28.2%) met inclusion criteria and were enrolled in the study. For 22 (12%) of them, standard laparotomic approach was preferred because of intraoperative surgeon evaluation. Thirty (16.3%) patients received the planned treatment of MI-IDS. Median age was 61 (range 39-81) years and median body mass index was 24 (range 20-31) kg/m2. Median numbers of NACT cycles was 4 (range 3-7). Median operative time was 285 (range 124-418) minutes and median estimated blood loss was 100 (range 50-200) mL. Surgical procedures included 28 (93.3%) hysterectomy and bilateral salpingo-oophorectomy, 29 (96.6%) omentectomy, 2 (6.6%) appendectomy, 11 (36.6%) regional peritonectomy, and 1 (3.4%) bowel resection. A residual tumor of 0 cm was reached in 29 (96.6%) patients and 0.5 cm in only 1 (3.4%) case. The vast majority of patients were discharged on postoperative day 2 (range 2-3). No early postoperative complications were registered. Median time to restart chemotherapy was 20 (10-30) days and all patients successfully completed the cycles. Histological findings showed 3 (10%) complete response, 9 (30%) microscopic residual disease, and 18 (60%) evidence of macroscopic residual disease. With a median follow-up of 10.5 month, 5 peritoneal and 2 lymph nodal recurrences were observed. Psychometric test revealed moderate discomfort in the vast majority of patients (66.7%). All patients are still alive. Conclusion Invasive-IDS in patients with clinically complete response to NACT seems to be feasible and safe in terms of perioperative outcomes, psycho-oncological impact, and survival rate. The equivalence between MI surgery and laparotomy needs to be confirmed with a longer follow-up and a larger number of patients.