OBJECTIVES: Medicare Part D beneficiaries who do not qualify for low-income subsidies (LIS) face high and variable cost sharing for specialty drugs during the calendar year.  We examined the magnitude of Part D cost sharing and out-of-pocket (OOP) cost patterns among non-LIS specialty drug users.  METHODS: Data were extracted from the 2012 Chronic Conditions Data Warehouse 100% Medicare claims.  The sample included non-LIS Medicare beneficiaries with 12 months of fee-for-service and stand-alone Part D plan coverage; a diagnosis of rheumatoid arthritis (RA), multiple sclerosis (MS), or selected cancers (i.e., multiple myeloma, chronic myeloid leukemia, advanced renal cell carcinoma); and a prescription fill for a Part D specialty drug indicated for these conditions in January 2012.  Annual cumulative OOP costs and OOP costs by calendar month for these specialty drugs were calculated for each disease area and overall.  RESULTS: Our sample consisted of 13,109 specialty drug users (N=3,826 for RA, N=3,931 for MS, N=5,352 for cancer).  The mean total annual OOP cost for specialty drugs across all diseases was $4,574 (RA $2,995, MS $4,425, cancer $5,807).  A significant proportion of MS (16%) and cancer (69%) specialty drug users had annual OOP costs ≥$5,000.  Overall, specialty drug users had to bear one-quarter to nearly one-half of their annual OOP costs in January alone (RA $781 [26%], MS $1,460 [33%], cancer $2,553 [44%]).  Even after entering catastrophic coverage, beneficiaries on average paid $2,095 out-of-pocket during the remainder of the year.  Sensitivity analyses in a subsample of patients who filled specialty drugs regularly during the entire year indicated even higher OOP burden.  CONCLUSIONS: The Part D cost sharing structure creates substantial financial burden for specialty drug users, especially in the beginning of the calendar year. Our findings suggest the need for changes in Part D including creation of annual OOP maximums and greater consistency in monthly OOP costs.