OBJECTIVES: To compare costs associated with healthcare resource use in patients with advanced renal cell carcinoma (RCC) receiving first-line treatment with pazopanib versus sunitinib. METHODS: COMPARZ was a multi-country, randomized, open-label, phase III study which demonstrated non-inferiority of pazopanib compared to sunitinib in adult patients with advanced RCC and no prior systemic therapy. Treatment continued until disease progression, unacceptable toxicity, withdrawal of consent, or death. We estimated total costs by combining non-protocol healthcare resource use with standardized price weights from a US claims database, and tracked from treatment initiation to study endpoint. Unadjusted and adjusted cost data were compared using univariate parametric (t-test) and non-parametric (Kaplan Meier Sample Average [KMSA]) tests to account for skewness and right-censoring. We estimated 80% power to detect a difference of $8,000 in total costs (two-sided test), assuming α = 0.05. Additional analyses were performed to account for non-normal distribution of the data. RESULTS: A total of 906 out of 1,110 enrolled subjects (N=454 pazopanib and N=452 sunitinib) reported resource use data. Mean follow-up was 10.6 months. Both arms were balanced at baseline for clinical and demographic characteristics. The population was 73% male, mean age of 61 and good performance status (76% had Karnofsky score 90-100). Rates of emergency visits/hospital days, provider contacts, diagnostics, and procedures were greater for patients receiving sunitinib compared to pazopanib. Mean costs were $12,120 for pazopanib-treated patients and $15,727 for sunitinib-treated patients (p=0.02), a difference of 29.7%. KMSA-derived costs were $21,026 for pazopanib and $29,043 for sunitinib. Cost differences between arms were significant when using Ordinary Least Squares and Generalized Linear Model approaches to adjust for region. Determinants of the difference in total costs include hospital expense and drug price. CONCLUSIONS: In a large, randomized trial in RCC, patients receiving pazopanib were less expensive compared to patients receiving sunitinib.