OBJECTIVES: To examine and compare costs and cost drivers for various metastatic renal cell carcinoma (mRCC) drugs. METHODS: This retrospective cohort study used administrative healthcare claims from MarketScan^® Commercial and Medicare Supplemental Databases to identify patients newly diagnosed with mRCC (index event) from 1/1/2006 to 3/31/2014, with continuous health plan enrollment at least 6 months prior to and 30 days following the index date. Treatment with approved mRCC products on or after the index date was required. Patients were followed until death, health plan enrollment end, initiation of non-mRCC chemotherapy, or study end. Healthcare costs reflect paid amounts to providers and out-of-pocket costs to patients.  Bootstrapping was used to determine differences between costs of drugs. RESULTS: The study population included 3060 mRCC patients. Total per-patient-per-month costs for pazopanib ($14,486) and sorafenib ($13,841) were not statistically lower at an alpha level of 0.05 than sunitinib ($15,808). However, temsirolimus ($19,431) and IL-2 ($96,619) were significantly more costly than sunitinib. For inpatient and patient out-of-pocket costs, IL-2 was significantly more costly than sunitinib. Outpatient costs of pazopanib and temsirolimus were both significantly more costly than sunitinib while sorafenib was significantly less costly. Multivariate modeling found that year of index date, number of metastatic sites, NCI comorbidity index score, and evidence of an adverse event during first line treatment were significantly associated with greater costs for all patients. In general, approximately 46% of total costs were specific to mRCC drug costs while 30% were due to inpatient stay. CONCLUSIONS: This study demonstrates that there may be significant cost differences between mRCC drugs and that mRCC drug costs represent the largest driver of total healthcare costs in this patient population. Further research on comparative effectiveness, weighing costs relative to clinical benefit, is needed.