Objective Recent economic and health policy changes may have affected the ability of chronically ill patients to afford their medications. We assessed changes in cost-related nonadherence to medication (CRN) before and after the implementation of Medicare Part D in 2006. Methods We used data from the National Health Interview Survey, an annual, population-based survey of community-dwelling, noninstitutionalized US adults, to estimate CRN in 8,673 stroke survivors aged 45 years or older, representing 4.8 million survivors, for the years 1999 to 2010. The main outcome measure was CRN, defined as self-reported inability to afford prescribed medication within the past 12 months. Results During the period 1999 to 2010, 11.4% of stroke survivors, approximately 543,000 individuals, reported CRN. From 1999 to 2010, CRN more than doubled among stroke survivors aged 45 to 64 years (from 12.7 to 26.5%; ptrend = 0.01). CRN remained stable among those aged 65 years or older (from 3.8 to 7.0%; ptrend = 0.21). From 1999?2005 to 2006?2010, CRN among uninsured stroke survivors aged 45 to 64 years increased from 43.1 to 57.1% (p = 0.03). Among stroke survivors aged 65 years or older with Medicare coverage, CRN was higher among Medicare Part D participants than those without the drug benefit (7.9 vs 4.8%; p = 0.02). After adjustment for sociodemographic and clinical factors, CRN was similar among Medicare Part D enrollees and nonenrollees. Interpretation From 1999 to 2010, CRN increased significantly among stroke survivors younger than 65 years, particularly among those without health insurance. There was no evidence that Medicare Part D decreased CRN among stroke survivors with Medicare. ANN NEUROL 2013;73:180?188