The completion and proper assessment of prospective, randomized controlled trials is essential for best medical practice. However, even though randomized trials are generally considered the pinnacle of evidence-based medicine, they are not infrequently poorly designed, implemented with inadequate quality control, and/or are subject to inappropriate interpretation or generalization, resulting in suboptimal clinical care and/or future investigative directions. The present report describes the most common and egregious misrepresentations from randomized trials, many of which may be attributed to the fallacies that arise from underpowered studies, resulting in overly optimistic or unwarranted conclusions. Caution is necessary when assessing composite outcomes, secondary end points, subgroup analyses, and the results of meta-analysis and meta-regression. Sponsors and investigators must accept responsibility for optimizing the design and execution of clinical trials, and practitioners, guidelines committees, editors, and regulators must critically interpret the data and literature arising from such studies. It is hoped that the principles embodied in the present commentary will spur improved design of future randomized trials and thoughtful critical appraisal by health care providers.