The What Works Clearinghouse (WWC) Study Review Protocol accompanies the "WWC Procedures and Standards Handbook, Version 5.0" and guides reviews of studies by the WWC. The WWC uses this protocol to review all studies, including those cited as evidence for U.S. Department of Education grant competitions, studies that were funded by the Department, and studies identified for systematic reviews of evidence based on a search of the research literature in a particular topic area. When the Study Review Protocol is used to review studies for systematic reviews, an accompanying topic area synthesis protocol will provide criteria for the literature search; guidance on how to identify and prioritize relevant studies for review and inclusion in evidence synthesis products; and guidance on intervention, sample, and outcome eligibility criteria for the synthesis. This protocol updates the "Study Review Protocol, Version 5.0" to clarify outcome domains and to formalize guidance and clarifications to the Handbook shared through the WWC Help Desk. Review teams should use the Version 5.1 "Study Review Protocol" for all new reviews conducted under Version 5.0 standards, except for systematic reviews already in progress.