OBJECTIVE: To determine proton pump inhibitor (PPI) treatment patterns and their affect on gastroesophageal reflux disease-related costs. METHODS: This study used claims data to identify continuously enrolled GERD-diagnosed subjects newly treated with a proton pump inhibitor (PPI) between 10/1/99 and 3/31/00. Data were analyzed for six months following PPI initiation. Results were stratified by first PPI filled during the study period. Compliance (measured by possession ratio), dosage escalation (>25% of initial dose), and daily average consumption (DACON) were measured. Subjects were assigned to one of four GERD severity groups based on ICD-9 diagnosis codes. Regression analysis was performed on GERD-related costs using treatment patterns and type of PPI drug as covariates of interest. Confounders including GERD severity were controlled for in the analysis. RESULTS: Of 75,452 subjects, there were 51,232 (67.9%) lansoprazole, 22,829 (30.3%) omeprazole and 1,391 (1.8%) rabeprazole subjects. Possession ratio was not significantly different by drug. Only 3.5% of rabeprazole subjects escalated versus 5.5% of omeprazole subjects and 9.3% of lansoprazole subjects (p=0.0001). Among subjects with esophageal ulcer or hiatal hernia, rabeprazole users had a significantly lower final DACON (1.03) versus both lansoprazole (1.20) and omeprazole subjects (1.22, p=0.0299). From the regression models, subjects who were compliant with therapy (ratio > 0.80) had 43% higher GERD-related pharmacy costs and 33% higher GERD-related total costs (both p<0.001). GERD-related medical costs were not significantly affected by compliance. Subjects who filled lansoprazole had 9.4% higher GERD-related pharmacy costs versus rabeprazole subjects (p<0.01). Omeprazole subjects had 12.5% higher GERD-related total costs versus rabeprazole subjects (p<0.01), while lansoprazole subjects had 18% higher GERD-related total costs versus rabeprazole subjects (p<.001). CONCLUSIONS: Rabeprazole subjects had lower GERD-related costs, less escalation and lower DACON compared to lansoprazole and omeprazole subjects. Compliance was not significantly different between drugs, nor did it decrease GERD-related costs.