Despite advancements in treatment modalities, the 10-year survival rate of women diagnosed with advanced-stage ovarian cancer has remained between 10% and 15% for the past 20 years. This is in part due to the majority of cases being diagnosed when disease has reached International Federation of Gynecology and Obstetrics stages III to IV. Approximately 70% of patients treated with cytoreductive surgery (CRS) and platinum-based chemotherapy experience recurrence within 18 months. The OVHIPEC trial, a randomized phase III trial found improved recurrence-free survival and overall survival with the addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to interval CRS. This study aimed to conduct a cost-effectiveness analysis (CEA) to determine the incremental cost-effectiveness ratio (ICER) of treatment with a combination of interval CRS and HIPEC compared with interval CRS alone in patients with stage III ovarian cancer. Data for the CEAwere extracted fromthe OVHIPEC trial (n = 245), which compared survival outcomes for patients with stage III ovarian cancer receiving either combination therapy (n = 122) or interval CRS alone (n = 123). Treatment costs from diagnosis to the time of disease recurrence were calculated using the treatment schedule in the OVHIPEC trial. Unit costs for disease-related procedures and events such as hospital admissions were calculated from multiple sources including national registries. All costs were initially retrieved in 2017 euros or converted to 2017 euros using the inflation rate established by the Consumer Price Index. Three different treatment protocols were analyzed: (1) standard chemotherapy, considered carboplatin and paclitaxel and/or gemcitabine and/or doxorubicin; (2) carboplatin-gemcitabine-bevacizumab and maintenance bevacizumab for platinum-sensitive disease; (3) maintenance poly (ADP-ribose) polymerase inhibitors for high-grade serous recurrent disease. The Makov model built to perform the analysis consisted of 3 mutually exclusive health states with corresponding utilities: Recurrence-free survival, disease recurrence, and death. The duration of each cycle in the model was 3 months, and a 10-year time duration was selected. The difference between the 2 groups in terms of qualityadjusted life-years (QALY) and incremental mean costs was calculated using 1000 replicas, made by extrapolating data from OVHIPEC survival outcomes, representing women at 60 years of age. The primary outcome for this trial was the ICER, calculated by dividing the mean incremental costs by the mean incremental QALY. Mean health care costs of interval CRS and HIPEC were €85,791 (95% credibility interval [CrI], €78,776-93,935) compared with €70,046 (95% CrI, €64,016-€76,661) for the interval CRS group. Treatment with interval CRS and HIPEC resulted in mean life-years of 5.07 (95% CrI, 4.80-5.34) compared with 4.07 (95% CrI, 3.83-4.33) for the interval CRS group. Adjusting for health-related quality-of-life data from the OVHIPEC trial, the mean QALY for the interval CRS and HIPEC group was 2.68 (95% CrI, 2.11-3.28) compared with 2.12 (95% CrI, 1.66-2.64) in the CRS group. The results showed an ICER of €28,299 per QALYover the first 5 years for patients treated with CRS and HIPEC. Probabilistic sensitivity analysis showed the likelihood of interval CRS combined with HIPEC being cost-effective was 83% using the Dutch WTP threshold of €80,000 per QALY. These results show that treatment with interval CRS and HIPEC shows a robust incremental QALY benefit compared with CRS alone. The probabilistic sensitivity analysis found that treatment with this combination therapy falls within the accepted values for cost-effective treatment costs in the Netherlands.