Background: Few studies compare targeted treatments for renal cell carcinoma (RCC) so understanding real world treatment patterns and healthcare utilization may inform decision making. This study evaluated treatment naïve RCC patients initiating sunitinib (SUN) or pazopanib (PAZ) and the potential impact of administration schedules on duration of therapy (persistence) assessments using claims data. Methods: This retrospective cohort analysis used de-identified Truven MarketscanMedicare Supplemental claims data. Included patients were ≥20 years, diagnosed with RCC with ≥1 prescription (Rx) for SUN or PAZ between Oct. 2009–Sept. 2013 and continuously enrolled ≥6 months prior to and 12 months after index. Patient characteristics, treatment patterns, persistence, RCC-related and all-cause costs were evaluated. Chi-square, Student t-test, or Wilcoxon signed-rank test were used to compare groups (α=0.05). A generalized linear model was used to evaluate costs controlling for patient demographics and characteristics, index medication dose, persistence and index medication. As the recommendation for most patients receiving SUN is 4 weeks on, 2 weeks off, a sensitivity analysis was conducted imputing 42 days supply (DS) for SUN Rx with 28 or 30 DS. Results: 291 patients initiated SUN (76.6%) and PAZ (23.4%). There were no significant (NS) differences between groups in demographics, Charlson Comorbidity Index scores, or proportion with pre-index inpatient admission. Mean time from earliest RCC diagnosis to index was longer for PAZ compared to SUN (518 vs. 398 days, p<0.05). There was NS difference in mean persistence in the non-imputed (154 vs. 175 days, p=0.20) and imputed DS (182 vs. 175, p=0.69) analyses for SUN and PAZ, respectively. Adjusted mean RCC-related ($65,993 vs. $65,254, p=0.68) and all-cause ($92,121 vs. 87,962, p=0.18) costs were NS different between SUN and PAZ cohorts, respectively. Conclusions: This analysis indicates NS differences in treatment persistence or costs for Medicare Supplemental patients with RCC initiating SUN or PAZ. Understanding the implications of SUN’s dosing schedule on DS values for persistence and other calculations is critical.