OBJECTIVES: The aim of this study was to explore the predictors of PPI dosing regimen [once daily (QD) or twice daily (BID)] among patients with GERD. METHODS: Using the HealthCore Integrated Research Database from 01/01/2004-06/30/2009, GERD patients (ICD-9 codes 530.10-530.13, 530.19, 530.81, or 787.1x), ≥ 18 years of age, having at least two PPI pharmacy claims (index date) from 01/01/2005-06/30/2008 and continuous eligibility for 12 months before and after the index date were identified. Based on the PPI dosing regimen throughout the post-index period, calculated as the ratio of quantity of medication dispensed/number of days supply, GERD patients were classified as QD (ratio of < 1.5) or BID (ratio of ≥ 1.5) PPI users. Descriptive analyses were used to compare QD vs. BID PPI users and a multivariate logistic regression was conducted to assess independent predictors of BID PPI use.  RESULTS: This study included 248,386 GERD patients with a mean age of 52.8 (+13.93) years and 56% were females. Based on the dosing regimen, 90% (n=222,759) were classified as QD and 10% (n=25,627) as BID PPI users.  Patients with BID PPI dosing were significantly (all p<0.0001) more likely to have Barrett’s Esophagus (5% vs. 2%), baseline H2RA use (8.7% vs. 6.8%) and higher comorbidity based on mean Deyo Charlson’s Comorbidity Index score (DCI) [0.89 (SD=1.54) vs. 0.70 (SD=1.37)].  Logistic regression results demonstrated that females [OR=1.13 (95% CI=1.08-1.18)], a diagnosis for Barrett’s Esophagus [OR=2.08 (95% CI=1.84-2.36)], baseline H2RA [OR=1.29 (95% CI=1.20-1.39)] or PPI use [OR=1.67 (95% CI=1.59-1.74)] and higher DCI score [OR=1.09 (95%CI=1.08-1.10)] were significant (all p<0.0001) predictors of BID PPI use. CONCLUSIONS: Patients who have a diagnosis of Barrett’s Esophagus, had baseline use of PPI or H2RA therapy were found to be significant predictors of BID PPI dosing. Further studies understanding the differences in clinical and economic outcomes based on PPI dosing regimen should be undertaken.