Objective To determine the effectiveness of practice guidelines for proton pump inhibitor use at an academic medical center. Methods Patients initiated on intravenous (IV) pantoprazole therapy between July 2001 and May 2002 were evaluated prospectively for appropriateness of therapy. Pharmacists assessed clinical use, dosing strategy, administration route, and prescribing patterns. Results A total of 85 patients were evaluated. Only 25% of the patients were prescribed IV pantoprazole according to established institutional guidelines. The majority of therapy meeting guideline criteria were initiated on pantoprazole by the Gastroenterology service. Due to overuse of pantoprazole, prescribing guidelines were revised to specify indications with proven efficacy (erosive GERD, Zollinger-Ellison or other hypersecretory conditions, and upper gastrointestinal bleeding). Patients who received pantoprazole for stress ulcer prophylaxis, an unapproved indication, had therapy automatically switched to a histamine receptor antagonist. For patients who tolerated oral medications or enteral feedings, therapy was automatically converted to the oral dosage form. Conclusions Evaluation of institutional pantoprazole utilization revealed usage extending beyond indications with proven efficacy. Pharmacists and physicians collaboratively developed evidence-based practice guidelines; adherence to appropriate indications showed a 50% improvement.