SUMMARYBackground: The efficacy of proton pump inhibitors (PPIs) or histamine-2 receptor antagonists (H 2 RAs) prescribed as prophylaxis for NSAID-related upper gastrointestinal (UGI) toxicity is dependent upon patient adherence. Aim: To describe patient adherence to prophylactically prescribed PPIs and H 2 RAs in the clinical setting. Methods: We conducted a retrospective observational cohort study using the Integrated Primary Care Information Project database. The study population consisted of incident non-specific NSAID users prescribed a PPI or H 2 RA specifically as prophylaxis for NSAID-related UGI toxicity. Patients were classified as non-adherent if < 75% of days of NSAID use were covered by one of these agents, and as continuing users after discontinuation of NSAID use if they had a renewed prescription for these agents after their last NSAID prescription. Results: The study cohort comprised 784 patients: 374 with H 2 RAs, 405 with PPIs, and 5 with both PPI and