OBJECTIVES:  Increased availability of novel oral oncolytics has had important implications for the delivery, financing, and outcomes of cancer care. Oral oncolytics are typically covered under the prescription benefit and are increasingly being subject to high cost sharing, raising the question of whether high out-of-pocket costs may interfere with cancer treatment initiation. Our study is the first to examine this issue for a range of novel oral oncolytics and to use data from recent years wherein aggressive cost-sharing strategies have become more prevalent. METHODS:  Utilizing 2014-2015 Integrated DataVerse data, we examined patients with a new adjudicated prescription for one of 42 oral oncolytics. We examined associations between out-of-pocket costs for the index oncolytic prescription and abandonment (i.e., failure to purchase index adjudicated prescription, with no alternative oral or infusible oncolytic prescription obtained within 90 days) and delayed initiation (i.e., failure to purchase index adjudicated prescription but same or alternative oncolytic obtained within 90 days). We used logistic regressions controlling for sociodemographic, clinical, and treatment characteristics to estimate adjusted outcome rates. Extensive sensitivity and subgroup analyses were conducted. RESULTS:  The sample included 38,111 Medicare and commercial insurance enrollees. Risk-adjusted abandonment rates were higher among greater out-of-pocket cost categories: 9% for the ≤$10 group vs. 13% for the $50.01-$100 group, 29% for the $100.01-$500 group, 38% for the $500.01-$2000 group, and 45% for the >$2000 group, P<0.001 for all comparisons. Delayed initiation was also more frequent among patients in higher cost-sharing categories (3% in ≤$10 group vs. 19% in >$2000 group, P<0.001). Sensitivity and subgroup analyses by type of insurance, pharmacy, and cancer identified similar associations. CONCLUSIONS:  Higher cost sharing was associated with higher rates of prescription abandonment and delayed initiation of oral oncolytic prescriptions. Our findings suggest cost sharing as a substantial barrier to prompt initiation of lifesaving treatments.