BACKGROUND Proactive, post-authorization monitoring of drug safety and effectiveness is of increasing importance. Rivaroxaban is a Factor Xa inhibitor with multiple indications, including: treatment of venous thromboembolism (VTE) and prevention of recurrent VTE; stroke prevention in atrial fibrillation; and prevention of atherothrombotic events (when combined with antiplatelet therapy) following an acute coronary syndrome. Use, safety and effectiveness of rivaroxaban in real-life settings need to be monitored to understand its value and comply with regulatory requirements. OBJECTIVES To develop a pharmacoepidemiologic PASS programme to characterize post-authorization rivaroxaban use and relevant outcomes related to safety (intracranial, gastrointestinal, and urogenital haemorrhage) and effectiveness (myocardial infarction, ischaemic stroke and thromboembolic events). METHODS European sources of longitudinal observational healthcare data were identified that contained population-based data on demographics, comorbidities and co-medications. Additional studies were designed to capture drug utilization, safety and effectiveness data in primary and secondary care via physician questionnaire completed based on medical chart review. With an emphasis on the consistent definition of endpoints, protocols were developed and tailored for each study for submission to regulatory authorities and relevant ethics committees. RESULTS A PASS programme of 7 studies was designed. Rivaroxaban drug utilization, and safety and effectiveness, in comparison with standard of care, are being assessed using The Health Improvement Network (UK), the PHARMO Database Network (The Netherlands), the German Pharmacoepidemiological Research Database and the National Swedish Registries. The programme also includes 2 Specialist Cohort Event Monitoring studies to collect data on the initial treatment period in secondary care settings, and a complementary Modified Prescription-Event Monitoring study that evaluates long-term use in primary care. CONCLUSIONS This pharmacoepidemiologic PASS programme, with its unique and complementary approach, will monitor and characterize the real-life benefit–risk profile of rivaroxaban. A flexible design allows the accommodation of any new indications for rivaroxaban approved during the study.