OBJECTIVES: To compare health care costs between patients who switched from a branded proton pump inhibitor (PPI) to a generic PPI and vice versa. METHODS: We conducted a retrospective database analysis using commercial enrollees from a large US health plan from February 2008 to March 2010. Continuously eligible adult patients who had gastroesophageal reflux disease (GERD) or GERD-related conditions, and evidence of PPI use during February 2009 to September 2009 were included. The index PPI was defined as the first PPI prescribed during the identification period. The two cohorts in this study included patients who switched from a generic PPI to a branded index PPI versus patients who switched from a branded index PPI to a generic index PPI. Risk adjustment was performed using propensity score matching.  We controlled for age, gender, region, GERD severity, plan, pre-index Quan-Charlson comorbidity score (CCI), baseline daily average consumption (DACON), and baseline costs and utilization. RESULTS: A total of 9881 patients from each cohort were matched after propensity score matching. During the 6 months after the switch, there were no statistically significant differences between the two cohorts in terms of office visit costs, outpatient costs, emergency services costs, inpatient costs, and other costs., However, patients who switched to a generic PPI had lower pharmacy costs ($1919 vs. $2306, p<0.001). CONCLUSIONS: Although pharmacy costs are slightly lower for patients who switched from a branded to a generic PPI, there were no significant differences in other health care costs such as for office visits, emergency room services, and inpatient visits.