Background: Targeted therapies (TTs) extend survival in mRCC, but high out-of-pocket (OOP) costs may limit access. This is particularly true for oral TTs covered under Medicare Part D wherein patients without low-income subsidies (non-LIS) typically face 25%-33% coinsurance (initial coverage phase), followed by ~50% coinsurance (coverage gap phase), and then 5% coinsurance (catastrophic phase). On the other hand, LIS patients face nominal cost sharing of ≤ $5 under Part D. In contrast, infusible TTs are covered by Medicare Part B and available at low OOP costs to both groups given supplemental insurance. Methods: We used 2011-2013 100% Medicare claims to examine oral TT (sorafenib, sunitinib, everolimus, pazopanib, or axitinib) initiation rates among fee-for-service non-LIS RCC patients newly diagnosed with metastases in the liver, lung, or bone, as compared to their LIS counterparts. We also compared initiation rates for infusible TTs (temsirolimus or bevacizumab) across the two groups. Logistic regressions controlling for patient (e.g. age, gender, race, metastatic site, Charlson score, nephrectomy) and plan characteristics (e.g. Part D plan type and formulary coverage, prior authorization (PA) for oral TTs) were used to model initiation rates. Results: The final sample included 1554 mRCC patients (mean age 72 years, 60% male, 85% White, mean Charlson score 1.1). On average, 86% of oral TTs covered by the patient’s plan formulary were subject to PA. Non-LIS patients (n = 1080) were less likely than LIS patients (n = 474) to have an oral TT claim within 6 months of first metastases claim (25% vs. 37%; adjusted odds ratio [adj-OR] = 0.52, p < 0.001). Initiation rates of infusible TTs were similar across both groups (11% vs. 12%; adj-OR = 1.11, p = 0.687). Non-LIS patients were less likely to initiate any (oral or infusible) TT within 6 months of metastases diagnosis (33% vs. 45%; adj-OR = 0.45, p < 0.001). Extensive subgroup and sensitivity analyses showed consistent findings. Conclusions: High cost sharing was associated with reduced and/or delayed access to oral TTs under Medicare Part D. Lower initiation of oral TTs was not offset by an increase in use of infusible TTs.