OBJECTIVES: Medicare Part D improved the access and affordability of prescription drugs among Medicare beneficiaries, however, there is no published study to evaluate the impact of two part D plans, stand-alone prescription drug plans (PDPs) and Medicare Advantage prescription drug plans (MA-PDs), on medication affordability. The objective of this study was to compare the cost-related nonadherence (CRN) and medication affordability among elderly Medicare beneficiaries enrolled in PDPs and MA-PDs. METHODS: A retrospective cross-sectional study was conducted using the national representative sample of elderly beneficiaries from Medicare Current Beneficiary Survey. Annual rates of CRN (skipping or reducing doses, not obtaining prescriptions) and medication affordability (spending less on basic needs to afford medicines) were compared among PDPs and MA-PD enrollees. In the naïve regression models, we assumed that the choice of Part D plans was exogenous, and conducted logistic regression analysis. Two-stage residual inclusion (2SRI) models were also modeled to estimate endogeneity in the choice of Part D plans. RESULTS: Beneficiaries enrolled in PDPs were more likely to be older, female and white non-Hispanics. MA-PD enrollees had lower prevalence of comorbidities and obesity. PDP enrollees showed a significantly higher prevalence of CRN than MA-PD enrollees (12.4% vs. 9.3%, p<.001), while had a similar prevalence of forgoing basic needs to afford medicines (3.9% vs. 2.9%, p=0.06). In the naïve regression models, after adjusting for socio-demographics and clinical characteristics, PDP enrollees were more likely to report CRN (odds ratio [OR] 1.39, 95% confidence interval [CI] 1.14-1.69), but had similar likelihood in spending less on basic needs to afford medicines (OR 1.35, 95% CI 0.94-2.03). 2SRI models produced similar results. CONCLUSIONS: Beneficiaries enrolled in PDP were associated with higher CRN than those enrolled in MA-PDs. Given the importance of medication adherence in controlling chronic diseases, CRN should be explicitly addressed through improving economic access to medications.