OBJECTIVES: To perform a cost analysis comparing the management of adverse events (AEs) and their associated cost in current clinical practice of bevacizumab (BEV) + interferon alpha-2a (IFN) versus sunitinib (SUN) in patients with metastatic renal cell carcinoma (mRCC) in Spain. METHODS: A decision analytic model was developed to compare the costs derived from the management of 40 grade 3/4 AEs in patients with mRCC, using published data from published trials (BEV+IFN: Escudier B. Lancet 2007;370:2103-11. SUN: Motzer RJ. N Engl J Med 2007;356:115-24). The analysis was performed from the Spanish public hospitals perspective. Estimation of resources used in managing AEs was made through an Expert Panel. Cost evaluation (€, 2009 values) included direct medical costs: outpatient visits, diagnostic and laboratory tests, hospitalization stays, surgeries, and medication. Unitary cost data were collected from Spanish Data Base of Sanitary Costs 2009 and Catalogue of Medicinal Products. RESULTS: Average cost of managing the grade 3/4 AEs per patient was €568 for BEV+IFN and €940 for SUN. The per patient cost savings of €372 when using BEV+IFN corresponds to a relative saving of 40% when compared to SUN. The main drivers for SUN costs were related to the management of laboratory abnormalities, anaemia, mucosal inflammation, decline in ejection fraction, diarrhea, thrombocytopenia, rash, epistaxis, and vomiting. In comparison, the main costs for BEV+IFN were associated to the management of gastrointestinal perforation, bleeding, proteinuria, venous thromboembolic event, anorexia and anaemia. CONCLUSIONS: The costs of managing side effects of SUN treatment are significantly greater than those for BEV+IFN in Spain. When selecting treatment options, the management costs of these side effects may be an important factor to consider for healthcare payers.