OBJECTIVES: This study models the costs of mRCC treatment for selected targeted agents (AIs and mTORs) in 18 US community oncology clinics using medical resource utilization data collected from patient medical charts. METHODS: Data were abstracted for 297 non-trial mRCC patients ≥18 years, receiving sunitinib (n=131), sorafenib (n=119), bevacizumab (n=19), or temsirolimus (n=28) as first-line targeted agent.  Per-patient-per-month (PPPM) costs (2009 USD) were estimated for targeted agents, intravenous administration, other drugs, procedures, hospitalizations, and treatment of adverse events (AEs; including drugs, procedures, hospitalizations, and office visits for AE treatment).  Drug costs were estimated using Average Wholesale Price, procedure costs were based on US private insurance reimbursement, hospitalization costs were based on HCUP National Inpatient Sample discharge diagnosis charges and published average cost-to-charge ratio. RESULTS: Median treatment duration was 5.9 (sunitinib), 5.5 (sorafenib), 6.7 (bevacizumab), and 2.8 (temsirolimus) months.  Total PPPM costs (mean±SE) were $9,417.35±670.78 (sunitinib), $7,992.48±682.29 (sorafenib), $14,770.48±1,393.25 (bevacizumab), and $11,493.39±1,256.53 (temsirolimus).  AI drug costs comprised 64% (sunitinib, sorafenib), 79% (bevacizumab), and 55% (temsirolimus) of total PPPM cost.  AE treatment costs PPPM were $1,972.62±560.86 (sunitinib, 21% of total PPPM costs), $1,302.58±559.54 (sorafenib, 16%), $425.25±265.69 (bevacizumab, 3%), and $1,810.85±627.63 (temsirolimus, 16%).  Given the median treatment durations, total costs over course of first-line AI were estimated as $55,562 (sunitinib), $43,959 (sorafenib), $98,962 (bevacizumab), and $32,181 (temsirolimus), including intravenous administration costs of $2,497 (bevacizumab) and $2,111 (temsirolimus).  CONCLUSIONS: Targeted agent drug cost was a major contributor to the total healthcare PPPM costs in patients with mRCC, followed by AE treatment costs.  While AEs may be largely related to tolerability for sunitinib and sorafenib, AE treatment cost was as high as 21% and 16% of total cost.  This study is limited by small sample sizes for bevacizumab and temsirolimus.