OBJECTIVES: To estimate adherence with immunosuppressant medications in transplant patients served by a group of five specialty pharmacies and to assess the medical cost avoidance associated with improved adherence, where possible. METHODS: Prescription fill data were obtained from five specialty pharmacies for Medicare patients who had prescriptions filled from January 2005 to June 2005 for one of the following medications: azathioprine, mycophenolate mofetil, mycophenolic acid, and sirolimus. Patients were eligible for analysis if they had a prescription filled in both January and June. Medication possession ratios (MPRs) were calculated for each medication over the study period. Patients with MPRs > 0.8 were classified as adherent. Literature-based adherence estimates were obtained for comparison. The 2005 US Renal Data System Annual Data Report was used to gather clinical and economic outcome data for a decision analysis to determine whether differences in adherence resulted in potential cost avoidance associated with a rejected renal graft. RESULTS: In the 1,599 eligible patients, the estimated adherence rate was 84.2%, which was significantly higher than the literature-based estimate of 65% (p<0.01). After applying the adherence estimates to current Medicare cost estimates for functioning renal grafts and failed renal grafts, the estimated yearly cost in study pharmacy patients was $27,853 versus $32,003 using literature-based adherence estimates—a potential cost savings of $4,150 per patient per year. CONCLUSION: These findings suggest that the reduced risk of rejection associated with increased adherence with immunosuppressant agents translates into avoidance of significant costs associated with failed renal grafts. Compared to traditional mail-order or retail pharmacies, the service model used by the study pharmacies involves high levels of patient contact to promote adherence. Policies to ensure appropriate reimbursement, such as CMS's proposed pay-for-performance framework, would be an important step to support and promote optimal patient care.