Objective: Angiogenesis inhibitor therapies (oral sunitinib or sorafenib, or IV bevacizumab off-label) are currently available as treatments for RCC patients. However, IV therapy may impose additional burdens for patients such as time lost in travel to treatment facilities, infection risk from IV catheters and increased costs. The potential incremental cost by resource use category associated with IV vs. oral administration of selected angiogenesis inhibitor therapies for the treatment of RCC was evaluated. Methods: Patients with = 2RCC claims (ICD-9 189.0, 198.0) receiving sunitinib (n=244), sorafenib (n=234) or bevacizumab (n=106) were identified from a large US commercial health insurance claims database covering over 39 million people between January 2002 - December 2006. Patients were observed from their first angiogenesis inhibitor therapy claim until the last treatment date. Inpatient, outpatient and pharmacy costs (actual payments made by health plans) were calculated on a per-patient per-month (PPPM) basis over the treatment period with costs for the study drugs reported separately. Results: PPPM costs for bevacizumab were $5130 higher than PPPM costs for sorafenib and $3,261 higher than PPPM costs for sunitinib. Additionally, bevacizumab drug and IV administration costs accounted for 51% of the outpatient costs for those patients. Excluding drug and administration costs, bevacizumab patients still incurred higher PPPM outpatient services costs of $3956, compared with patients receiving sunitinib or sorafenib at $2913 and $2230 respectively. Monthly costs for inpatient services were also higher for bevacizumab patients ($2467) vs. sunitinib ($1716) and sorafenib ($1082) patients. Conclusion: RCC patients treated with bevacizumab incur an additional $39,132 - $61,560 total medical cost increase per patient per year compared to those treated with sunitinib or sorafenib. The development of more tolerable and efficacious oral angiogenesis inhibitor therapies may result in additional cost savings to patients and health care payers over IV therapies.