OBJECTIVES The increase in premium-priced orphan drugs coupled with health care budget constraints will pressure managed care plans to consider restricting market access. Coverage and reimbursement of the top ten selling FDA-designated orphan drugs (alglucerase, imiglucerase, imatinib, adalimumab, lamotrignine, lidocaine patch, modafinil, cinacalcet, buprenorphine/naloxone, topiramate) were analyzed for seven of the most populous Medicare managed care plans (Aetna, SilverScript, Coventry, Medco, Cigna, United HealthCare, Humana). METHODS The formulary tier structure, out-of-pocket costs (OPC) and utilization restrictions (UR)—pre-authorization (PA), quantity limits (QL) and step therapy (ST)—were obtained from CMS (www.medicare.gov). Orphan drugs analyzed were the top ten in 2007 retail sales (SDI VONA). OPC was reported as a percentage of the drugs' costs paid by patients, determined by averaging initial, gap, and catastrophic coverage levels. RESULTS Among the seven plans covering the ten drugs, PA was the most common UR (40.0%), followed by QL (35.7%) and ST (2.9%). Alglucerase, the 3rd most expensive drug, had the highest OPC (59.9%) on average among all seven plans. Modafinil, the 4th least expensive, had the lowest OPC (40.3%) on average. However, modafinil was subjected to utilization restrictions by all plans studied and most frequently overall (13 of 21 possible restrictions; 61.9% OPC) while alglucerase, lamotrignine (3rd least expensive), buprenorphine/naloxone (5th least expensive) were the least frequently restricted (14.3% each). Medco had the highest OPC for the ten drugs (52.9%) while SilverScript had the lowest (40.1%). Coventry employed URs most frequently (53.3%) while SilverScript used them least frequently (6.7%). CONCLUSIONS Orphan drugs do not appear to be immune to market access limitations. URs on orphan drugs were prevalent in the most populous plans, with patients bearing 40-60% of the drugs' costs out-of-pocket. The extent of restrictions was not proportional to the drugs' price, suggesting that more research is warranted to investigate myriad factors related to orphan drug access.