OBJECTIVES: The purpose of the study is to evaluate the impact of a tablet splitting program in a large pharmacy benefit management organization on the costs and utilization of prescription drugs. METHODS: Using a retrospective cohort study design, prescription records from January 1, 2005 to June 30, 2005 were obtained from a pharmacy claims database. Three study cohorts— voluntary, mandatory, and control cohort were created based on the enrollment status in the tablet splitting program. The number of prescriptions dispensed, the total costs and savings per prescription were analyzed and compared for the study drugs Lexapro, Lipitor, and Zoloft. RESULTS: A total of 606,068 prescriptions, 594,825 in the control, 5,226 in the mandatory and 6,017 in the voluntary cohort were included. Total cost savings were obtained by subtracting the difference in cost/days supply between drugs in the control group and each active treatment group. Total cost savings are at $179,575.85 and $74,119.53 for the mandatory and the voluntary cohort respectively after adjusting for the operation costs and subtracting the costs from the treatment cohorts. An average per prescription cost saving of $34.36 for the mandatory and $12.31 for the voluntary program was realized for the three drugs studied. CONCLUSION: A tablet splitting program has been shown to produce significant savings, $34.36 and $12.31 per prescription for the health plan enrolled in the mandatory and voluntary programs respectively.