Objective In the hospital setting, several studies have reported proton pump inhibitor (PPI) overuse, a majority of which is continued after discharge. In addition to being expensive, PPIs are associated with an increased risk of infections, osteoporosis and serious drug interactions. We examined the trends and predictors of PPI guidelines non-compliance among academic and non-academic hospitalists in USA. Methods and Patients Oral PPI prescriptions initiated by 2 academic and 2 non-academic hospitalist groups were reviewed. Prescription indications were recorded when explicitly stated in the chart. Otherwise, qualified physicians reviewed the chart to make such determination. Indications were then compared to the published guidelines. Several variables were tested to determine independent predictors of initiation and post discharge continuation of guideline non-compliant prescriptions. Results Of the 400 PPI prescriptions 39% were guideline compliant. Academic hospitalists were significantly more compliant with PPI prescription guidelines (50 vs 29%). Gastrointestinal ulcer bleeding prophylaxis (GIP) for low risk patients was the most common indication for non-compliant prescriptions, while that of guideline compliant prescriptions was dyspepsia treatment. Independent predictors of the initiation of guideline non-compliant prescriptions were non-academic hospitalist group, PPI indication not documented in the chart, and GIP as part of the admission orderset. The latter was an independent predictor of those prescriptions continuation post-discharge (protective) in addition to non-academic hospitalists group. Conclusion Hospitalists overprescribe PPI to a level comparable to that of the non-hospitalist providers in the literature. Understanding the determinants of increased compliance among academic groups is instrumental to design interventions aimed at increasing PPI prescription compliance.