OBJECTIVES: The incidence of AEs and the costs associated with the management of those AEs have not been widely studied in patients with RCC receiving bevacizumab, sorafenib, or sunitinib.  This study evaluates these outcomes using a large claims database. METHODS: Patients with ≥ 2 RCC claims (ICD-9 189.0, 198.0) were identified in a large US commercial insurance claims database from 1/02 through 12/08.  Patients were observed and analyzed during the time of their first AI treatment with bevacizumab, sorafenib, or sunitinib.  AEs were defined as diagnoses that were treatment-emergent (i.e., diagnoses not present in the 6 months prior to initiation of AI treatment).  The incidence rate (IR) and mean cost per visit for each AE were calculated in the outpatient, inpatient and ER settings.  Cost data represented actual payments made by insurers. RESULTS: The inclusion criteria identified 269 bevacizumab, 375 sorafenib, and 672 sunitinib patients.  The three most frequent AEs experienced by patients in each treatment group were identified based on the overall IR.  The setting-specific IRs and costs per visit for these AEs are: bevacizumab: outpatient=20.3/$1,522, 16.1/$652, 11.6/$91; inpatient=3.9/$8,222, 1.5/$15,848, 1.4/$4,808; ER=3.8/$643, 0.7/$24, 0.8/$176 for anemia, lung diseases, and hypertension, respectively; sorafenib: outpatient=24.1/$525, 19.2/$226, 11.0/$288; inpatient=1.1/$8,205, 3.7/$6,104, 1.6/$18,001; ER=0/$0, 2.3/$218, 10.3/$294 for lung diseases, hypertension, and abdominal pain, respectively; sunitinib: outpatient=31.1/$176, 26.5/$990, 23.3/$1,183; inpatient=3.7/$13,183, 0.4/$30,843, 2.7/$13,727; ER=7.6/$409, 0/$0, 2.0/$606 for hypertension, lung diseases, and anemia, respectively. For outpatient treatment, there was a trend for IRs for each of the AEs to be the highest for sunitinib. CONCLUSIONS: Bevacizumab, sorafenib, and sunitinib were associated with frequent AEs, in particular abdominal pain, anemia, hypertension, and lung diseases.  Management of these and other AEs resulted in significant medical treatment costs.  These results can be used in economic evaluations of various currently available targeted therapies for RCC.