OBJECTIVES The combination of BEV + interferon-alpha2a (IFN) prolongs progression-free survival compared with IFN + placebo [Escudier, Lancet 2007], providing comparable efficacy to sunitinib in patients with mRCC. Notably, the type and frequency of side effects differ between the two regimens. When selecting treatment options, the management of side effects and associated costs are important factors to consider for physicians and healthcare payers. A previous report showed that grade 3/4 adverse events (AEs) account for the majority of side-effect management costs [Mickisch, ASCO 2008]. We report here the results of an updated analysis of grade 3/4 AE management costs for BEV + IFN and sunitinib. METHODS A linear decision analytic model was developed to compare the management costs of grade 3/4 AEs of BEV + IFN and sunitinib from the perspective of healthcare purchasers or hospital-based care in Germany, France, the UK and Italy. Data sources included published cost literature and clinical trials, official price/tariff lists and country-specific cost databases. RESULTS The grade 3/4 AE management costs for sunitinib were higher than those for BEV + IFN in Germany (€1785 vs €1367), France (€2590 vs. €1618), UK (€1475 vs. €804) and Italy (€891 vs. €402). The main cost drivers were country dependent, but in general were lymphopenia, leucopenia, neutropenia, thrombocytopenia and fatigue/asthenia for sunitinib; the main cost drivers for BEV + IFN were proteinuria, fatigue/asthenia, bleeding, anaemia and gastrointestinal perforation. The difference in management costs between the two regimens was mainly due to the higher incidence of haematological side effects with sunitinib compared with BEV + IFN and their associated high management costs. CONCLUSIONS The costs of managing AEs of sunitinib are greater than those for BEV + IFN in Germany, France, UK and Italy. AE profiles are therefore an important consideration when selecting treatments for mRCC.