Background: The addition of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) to interval cytoreductive surgery improves recurrence-free and overall survival in patients with FIGO stage III ovarian cancer who are ineligible for primary cytoreductive surgery due to extensive intraperitoneal disease. The effect of HIPEC remains undetermined in patients who are eligible for primary cytoreductive surgery. We hypothesize that the addition of HIPEC to a complete or near-complete (residual disease ≤2.5 mm) primary cytoreductive surgery improves overall survival in patients with FIGO stage III ovarian cancer. Methods: This international, randomized, open-label, phase III trial enrolls patients with newly diagnosed, histological proven FIGO stage III epithelial ovarian, fallopian tube, or primary peritoneal cancer. Patients with resectable umbilical, spleen or local bowel lesions may be included. Following complete or near-complete primary cytoreduction, patients are intra-operatively randomized (1:1) to receive HIPEC or no HIPEC. Patients in both study arms will receive six courses of adjuvant carboplatin-paclitaxel and maintenance PARP-inhibitor or bevacizumab according to current guidelines. The primary endpoint is overall survival. To detect a Hazard Ratio of 0.67 in favor of HIPEC, 200 overall survival events are required. Assuming that accrual will be completed in 60 months, and 12 months additional follow-up, 538 patients need to be randomized. All randomized patients will be included in the analysis for overall survival according to the intention to treat principle. Pre-specified subgroup analyses will be performed based on stratification factors (peritoneal cancer index at start of surgery, completeness of surgery), histologic subtype (high-grade serous versus other), and BRCA mutation (BRCA1/2 mutation versus wildtype). Secondary endpoints are recurrence-free survival, time to first subsequent anticancer treatment, and treatment related complications and toxicity. Exploratory endpoints are time to second subsequent anticancer treatment, health-related quality of life, and cost-effectiveness. The Institutional Review Board of the Netherlands Cancer Institute approved the trial, which is actively enrolling patients since January 2020. Clinical trial information: NCT03772028