This article provides an evidence-based medicine framework to critically assess the validity of study design and clinical significance of study results in the context of gastrointestinal therapies for a common clinical scenario. Without systems for critically appraising and applying clinical research, we may become dependent on outdated information. When used in conjunction with clinical judgment, critical appraisal of clinical research facilitates the provision of the very best care to patients. This article, which examines a trial about the gastrointestinal safety of cyclooxygenase (COX)-II-selective nonsteroidal anti-inflammatory drugs (NSAIDs), follows the format of other evidence-based medicine articles in the Canadian Medical Association Journal, the Journal of the American Medical Association, and Gastroenterology. The evidence-based medicine concepts have been expanded from previous articles and examples from the gastrointestinal literature have been used.