OBJECTIVES: . Observational studies are often planned on an ad hoc basis, with the risk that methods are inconsistent and that aims overlap rather than complement each other. Our objective was to develop a systematic approach for identifying observational data sources for an integrated global programme of real-world evidence gathering, to support an important new indication for an antiplatelet drug. METHODS: . Systematic literature and Web searches, supplemented with email and telephone contact with data owners, were used to identify and characterize registries and healthcare databases suitable for use in observational studies of myocardial infarction and acute coronary syndromes. The ability to identify patients across data sources was also assessed. Data were captured and evaluation criteria applied, including compatibility with aspects of an ongoing randomized clinical trial (patient population, treatments, outcomes, and length of follow-up [≥3 years]). Selection criteria included accessibility; availability of inpatient, outpatient, cardiac event, and drug data; and generalizability. RESULTS: . Over 2700 publications were screened; we identified 216 registries and 380 databases (primarily of administrative claims and electronic medical records). Of these, 12 registries, and 21 databases met the evaluation criteria and were assessed in depth. After application of the selection criteria, 5 registries and 12 databases were recommended. Recommended data sources ranged in size, each capturing data on between 4000 and 11 million patients, and were geographically diverse, representing populations in Europe, the USA, and Australia. Each recommended data source had unique strengths and limitations for use in real-world evidence studies, and together they had the potential to provide consistent and complementary information. The study output provided a valuable tool for global and local investigators. CONCLUSIONS: . Observational data sources are diverse. A systematic understanding of real-world evidence can guide the development of a coherent strategy for designing observational studies to support clinical research.