OBJECTIVES: The objective of this study was to estimate per patient per month (PPPM) costs of medications in the six Medicare Part D protected classes based on findings among Medicare and dual eligible beneficiaries with drug coverage prior to enactment of the benefit. METHODS: Data were from the Thomson Medstat Marketscan Medicare and Medicaid claims databases. The study sample was constructed by identifying patients who were enrolled either in Medicare or dually in Medicare and Medicaid in 2004. Costs were aggregated within each class, including patient-paid and plan-paid amounts. These costs provided the numerators for the PPPM calculations. Denominators were defined as the aggregated patient months for only those individuals who filled a drug within a particular class. Drugs covered under Part B were excluded. RESULTS: The classes where generic formulations were available (antidepressants and anticonvulsants) showed lower PPPM costs ($45.31 and $50.97, respectively). The costliest class was the antiretrovirals ($1028.13) for dual eligible patients including those age 64 and under. Among the dual eligibles over 65, immunosuppressants were the costliest ($657.72). In the Medicare group, the cost of immunosuppressants ($814.86) was substantially higher than the other five classes. The PPPM cost over all 6 classes for Medicare was $54.75, for dual eligibles it was $157.99, and $116.35 for all patients. CONCLUSION: PPPM costs were not uniformly high among the protected classes. The claims data in this study allowed a “real world” check of how much the protected classes may impact the finances of Part D. There are differences within the classes between the dual eligible and Medicare patients, and also within the dual eligibles by age. This is an important message to policy makers that a change to the structure of the protected classes in Part D may have differential effects across and also within classes.