OBJECTIVES: CheckMate-214 (NCT02231749) has demonstrated overall survival benefits and enhanced quality of life for nivolumab in combination with ipilimumab (N+I) relative to sunitinib as first-line (1L) treatment in patients with advanced or metastatic renal cell carcinoma (RCC) with intermediate or poor prognostic risk. The objective of this study was to conduct a cost-effectiveness analysis comparing N+I to sunitinib for 1L treatment of RCC in the Netherlands. METHODS: A three-state partitioned survival model was developed, with pre-progression, progressed disease, and death health states. Survival data were sourced from CheckMate-214 and extrapolated to a 30-year time horizon. Per clinician feedback, time on 1L treatment data were extrapolated up to 2 years to estimate costs related to drug acquisition and administration incurred by patients. Cost of nivolumab was based on list price. Utility estimates were derived from CheckMate‑214, and resource use for disease management was estimated based on the literature. Scenario analyses were conducted to explore key assumptions regarding survival extrapolations and health state utility estimates. RESULTS: Treatment with N+I was estimated to result in a mean discounted quality-adjusted life years (QALYs) gain of 5.0 over a 30-year time horizon. Treatment with sunitinib was estimated to result in 3.6 QALYs, yielding an incremental benefit of N+I versus sunitinib of 1.4 QALYs. Total costs were estimated at €311,359 and €236,000 for N+I and sunitinib, respectively. The incremental cost-utility ratio (ICUR) was estimated at €54,831 per QALY. Scenario analyses demonstrated that the selected survival extrapolations were conservative as most alternative extrapolations demonstrated higher net benefit for N+I. Alternative health state utility estimates had little impact on the health-economic results. CONCLUSIONS: In this model-based analysis, N+I was a cost-effective treatment option for the 1L treatment of RCC in the Netherlands. It would thus provide a valuable treatment option for a disease area with high unmet need.