Background: Avelumab in combination with axitinib (A+Ax) was approved by the FDA for the first-line (1L) treatment of patients with advanced renal cell carcinoma (RCC). We aimed to evaluate the financial impact of adding A+Ax as a 1L treatment option for patients with advanced RCC from a US payer perspective. Methods: A Microsoft Excel®-based model was developed to estimate the incremental budget impact of adding A+Ax as a 1L treatment option for patients with advanced RCC in 2019-2021 after the introduction of A+Ax in May 2019. The patient population was based on a hypothetical private health plan with 1 million members. Comparators for the model included pazopanib, sunitinib, cabozantinib, nivolumab+ipilimumab, high-dose interleukin-2, temsirolimus, and pembrolizumab+axitinib (Pem+Ax). Cost elements of the model included drug acquisition, administration, adverse event management, monitoring, and subsequent treatment. Model inputs were mostly obtained from published literature, prescribing information, or other public information. Utilization rates were assumptions, with no utilization for A+Ax or Pem+Ax prior to their introduction to the health plan. After their introduction, uptake of both A+Ax and Pem+Ax was assumed to be 3.4% in 2019, 7.3% in 2020, and 8.4% in 2021. Sensitivity analyses were conducted to assess the model uncertainty. Results: For a 1 million–member health plan, the estimated eligible patient population in the 1L advanced RCC setting was 46 patients in 2019 (prorated) and 79 in both 2020 and 2021. The incremental budget impact attributed to A+Ax was estimated to be $0.01, $0.05, and $0.07 in 2019, 2020 and 2021, respectively, on a per-member per-month (PMPM) basis, and $130,761, $621,548, and $867,391 in 2019, 2020, and 2021, respectively, on an annual basis. Stratifying the results by cost category showed treatment duration and drug acquisition cost to be the main drivers of budget impact. Sensitivity analyses demonstrated that the budget impact remained within a reasonable range across all scenarios. The widest ranges in 2021 are due to treatment duration: $0.01-$0.23 on PMPM and $68,178-$2,780,432 on annual total. Conclusions: The analysis showed a modest budget increase for payers from the introduction of A+Ax to private health plans for the 1L treatment of patients with advanced RCC. These results should be considered in the context of the clinical benefits of these new treatment options in this patient population.