Evidence-based medicine is an important initiative of the U.S. National Institutes of Health. However, published data are limited. Medical knowledge can be advanced through pharmacoepidemiology and data mining research of very large databases, data warehouses. Before Vioxx™ (rofecoxib) and Celebrex™ (celecoxib) were publicly suspected of being associated with acute myocardial infarction and stroke, etodolac was evaluated for gastrointestinal safety using a data warehouse constructed from several data sources and data mining tools embedded with pharmacoepidemiologic methods. Results were published in a top tier medical journal, and established gastrointestinal safety of a generic COX-2 analgesic medication. This project demonstrates that the knowledge needed for evidence-based medicine can be augmented through pharmacoepidemiology research using data mining and data warehousing.