BACKGROUND: In the largest overhaul to Medicare since its creation in 1965, the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 established Part D in 2006 to improve access to essential medication among disabled and older Americans. Despite previous evidence of a positive impact on the general Medicare population, Part D's overall effects on long-term care (LTC) are unknown. OBJECTIVE: The purpose of this systematic review was to evaluate the literature regarding Part D's impact on the LTC context, specifically costs to LTC residents, providers and payers; prescription drug coverage and utilization; and clinical and administrative outcomes. DATA SOURCES: Four electronic databases [PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Health Business Fulltext Elite and Science Citation Index Expanded], selected US government and non-profit websites, and bibliographies were searched for quantitative and qualitative studies characterizing Part D in the LTC context. Searches were limited to studies that may have been published between 1 January 2006 (date of Part D implementation) and 8 January 2013. STUDY SELECTION: Systematic searches identified 1,624 publications for a three-stage (title, abstract and full-text) review. Included publications were in English language; based in the US; assessed Part D-related outcomes; and included or were directly relevant to LTC residents or settings. News articles, reviews, opinion pieces, letters or commentaries; case reports or case series; simulation or modeling studies; and summaries that did not report original data were excluded. STUDY APPRAISAL AND SYNTHESIS METHODS: A standardized form was used to abstract study type, study design, LTC setting, sources of data, method of data collection, time periods assessed, unit of observation, outcomes and results. Methodological quality was assessed using modified criteria specific to quantitative and qualitative studies. RESULTS: Eleven quantitative and eight qualitative studies met inclusion criteria. In the seven years since its implementation, Part D decreased out-of-pocket costs among enrolled nursing home residents and potentially increased costs borne by LTC facilities. Coverage of prescription drugs frequently used by older adults was adequate, except for certain drugs and alternative formulations of importance to LTC residents. The use of medications that raise safety concerns was decreased, but overall drug utilization may have been unaffected. Although there was uncertain impact on clinical outcomes, quantitative studies demonstrated evidence of unintended health consequences. Qualitative studies consistently revealed increased administrative burden among providers. LIMITATIONS: Empirical evidence of Part D's LTC impact was sparse. Due to limitations in available types of data, quantitative studies were generically lacking in methodological rigor. Qualitative studies suffered from lack of clarity of reporting. As future studies use clinical Medicare data, study quality is expected to improve. CONCLUSION: Although LTC-specific policies continue to evolve, it appears that the prescription drug benefit may require further modifications to more effectively provide for LTC residents' unique medication needs and improve their health outcomes. Adjustments may be needed for Part D to be more compatible with LTC prescription drug delivery processes.