OBJECTIVES: The burden of metastatic renal cell carcinoma (mRCC) is substantial for patients and society. Bevacizumab (BEV) combination with interferon alfa-2a (IFN) has demonstrated to prolong mRCC patients’ progression-free-survival and to have comparable efficacy to sunitinib (SUN). However, tolerability differs between these treatment alternatives and it is therefore of importance to evaluate the economic impact of adverse events (AEs) management, for each alternative, in the daily clinical practice in Portugal. METHODS: A linear decision analytical model was applied considering direct medical costs only in the Portuguese Health System perspective. AEs incidences associated with each of the two alternatives were extracted from published literature. Health resource consumption was estimated based on an expert panel of Portuguese oncologists and urologists. Corresponding unitary costs were obtained through national official sources. The considered time horizon was one year. The base-case analysis includes all grades AEs and a normal dose (9 MUI, three times weekly) of IFN scenario. Deterministic univariate sensitivity analyses were performed to test the robustness of the model including grade 3-4 AEs analysis only and IFN low-dose (6 MUI or 3 MUI, three times weekly) scenarios. RESULTS: The associated costs of managing AEs were considerably lower with BEV+IFN than with SUN in Portugal. The average treatment costs for all grade AEs per patient was €1472 for SUN and €1093 for BEV+IFN resulting in a difference of -379 € (a cost-saving of 26% for BEV+IFN versus SUN). Sensitivity analyses showed that BEV+IFN remains the less costly option when alternative scenarios are considered and that a low-dose IFN would lead even to further cost-savings. CONCLUSIONS: BEV+IFN is a more tolerable and hence cost-saving alternative for the Portuguese Health System considering the AE management costs of mRCC treatment when compared to SUN. These results are consistent with previous evidence for other countries.