OBJECTIVES: To evaluate OTC Prilosec Step Care programs on the utilization and costs of Proton Pump Inhibitors (PPI) in a large pharmacy benefit management setting. METHODS: Using pre-post with control group study design, prescription records from January 1, 2003 to October 31, 2004 were obtained from pharmacy claims database in a large pharmacy benefit management organization. Clients were assigned to one of the four cohorts—formulary changes and step care, step care only, formulary change only, no formulary change and no step care (serves as the control group). The number of prescriptions dispensed and the total costs per member per month (PMPM) were analyzed and compared among the groups. RESULTS: From the pre to post period, in the cohort with formulary change and step care, the average number of prescriptions per month decreased by 50.2% and the average PMPM costs decreased by 55.8% (from $3.44 to $1.52). In the step care only cohort, the number of prescriptions decreased by 34% and the average PMPM costs decreased by 25.4% (from $4.2 to $3.13). In the formulary change only cohort, the number of prescriptions decreased by 12% and the average PMPM costs decreased by 22.7% (from $3.38 to $2.61). In the control group, the number of prescriptions decreased by 18.9%, while the average PMPM costs increased by 3.3% (from $4.06 to $4.19). OTC Prilosec Step Care programs resulted in PMPM and total annualized cost savings, $2.03 and $4,727,058 for the cohort with formulary change and step care, $1.21 and $757,915 for the cohort with step care only, $0.88 and $1,230,662 for the cohort with formulary change only. CONCLUSIONS: OTC Prilosec Step Care programs were found to be very effective in controlling the utilization and expenditures on PPIs.