Context:The popularity of running barefoot or in minimalist shoes has recently increased because of claims of injury prevention, enhanced running efficiency, and improved performance compared with running in shoes. Potential risks and benefits of running barefoot or in minimalist shoes have yet to be clearly defined.Objective:To determine the methodological quality and level of evidence pertaining to the risks and benefits of running barefoot or in minimalist shoes.Data Sources:In September 2013, a comprehensive search of the Ovid MEDLINE, SPORTDiscus, and CINAHL databases was performed by 2 independent reviewers.Study Selection:Included articles were obtained from peer-reviewed journals in the English language with no limit for year of publication. Final inclusion criteria required at least 1 of the following outcome variables: pain, injury rate, running economy, joint forces, running velocity, electromyography, muscle performance, or edema.Study Design:Systematic review.Level of Evidence:Level 3.Data Extraction:Two reviewers appraised each article using the Downs and Black checklist and appraised each for level of evidence.Results:Twenty-three articles met the criteria for this review. Of 27 possible points on the Downs and Black checklist, articles scored between 13 and 19 points, indicating a range of evidence from very limited to moderate. Moderate evidence supports the following biomechanical differences when running barefoot versus in shoes: overall less maximum vertical ground reaction forces, less extension moment and power absorption at the knee, less foot and ankle dorsiflexion at ground contact, less ground contact time, shorter stride length, increased stride frequency, and increased knee flexion at ground contact.Conclusion:Because of lack of high-quality evidence, no definitive conclusions can be drawn regarding specific risks or benefits to running barefoot, shod, or in minimalist shoes.