OBJECTIVES To examine PPI utilization among patients with non-erosive GERD (NERD), erosive esophagitis (EE) and Barrett's esophagus (BE). METHODS We conducted an observational cohort study using EMRs obtained from a fully integrated health delivery system located in the mid-Atlantic region of the US. Incident cases of BE, EE, and NERD were identified between July 1, 2004-January 25, 2007. Patients were required to have encounter data for 6 months before and 12 months following their index diagnosis. Frequency of PPI use, time to PPI initiation, dosing frequency, and switching patterns among the three cohorts at 52 weeks post diagnosis were compared using NERD as the reference group. RESULTS 12,273 patients met the inclusion criteria and included 79.6% NERD, 17.9% EE and 2.3% BE patients. A higher proportion of NERD and EE patients received a PPI as their initial pharmacologic therapy (90.5% and 92.2%; p=0.0140) compared to 70.5% (p<0.0001) of BE patients. Greater than 90% of NERD and EE (p<0.0001) patients started initial PPI therapy within 8 weeks post diagnosis compared to 71.6% (p<0.0001) of BE patients. Majority of patients were prescribed once daily PPI therapy [NERD 79.4%; BE 68.2% (p<0.0001); EE 73.6% (p<0.0001)] with a substantial proportion of patients on twice daily therapy [NERD 12.3%; BE 31.3% (p<0.0001); EE 15.2% (p=0.0003)]. Switching among initial PPI therapy occurred more often within BE patients (14.4%; p=0.0083) as compared to NERD and EE patients (9.0%, 9.3%; p=0.6896). There were no significant differences in patients reducing their PPI frequency from twice daily to once daily therapy (NERD 24.5%, BE 18.5%, EE 25.7%). CONCLUSIONS A substantial proportion of patients with GERD are on twice daily PPI regimen. Switching between various PPI agents is common among GERD patients. Future research should focus on the clinical and economic implications of twice daily PPI use and switching among PPIs.