OBJECTIVES: To examine the relationship between receiving the Medicare Part D low-income subsidy (LIS) and cost-related medication nonadherence (CRN). DESIGN: Cross-sectional. SETTING: Medicare Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey collected in spring 2007. PARTICIPANTS: Part D-enrolled Medicare beneficiaries who responded to the CAHPS survey. MEASUREMENTS: Respondents were categorized into three LIS groups: deemed LIS (Medicare and Medicaid dual-eligible and individuals receiving Supplemental Security Income), LIS applicants (other low-income individuals who applied for and received LIS), and non-LIS. Adjusted logistic models were used to assess the likelihood of CRN according to LIS status. Sample weights were applied in all analyses to account for complex sampling design. RESULTS: Of 171,573 Part D-enrolled respondents (weighted N = 14,572,827; response rate 48%), 17.2% reported CRN. Specifically, 14.7% of non-LIS respondents, 22.2% of deemed-LIS respondents, and 24.0% of LIS applicants reported CRN. LIS groups had higher unadjusted odds of CRN than the non-LIS respondents, but fully adjusted odds of CRN were lower in the deemed-LIS (adjusted odds ratio = 0.66, 95% confidence interval = 0.59, 0.74) than the LIS applicants or the non-LIS respondents. Subgroup analyses revealed that sociodemographic and health-related characteristics were associated with higher CRN in all three groups. CONCLUSION: The lower adjusted odds of CRN in deemed-LIS is reassuring, suggesting that autoenrollment provides meaningful assistance in removing cost-related barriers to medication use, but certain sociodemographic characteristics were associated with higher odds of CRN. Efforts to improving outreach to these subgroups and tracking of CRN are warranted.