The What Works Clearinghouse (WWC) systematic review process is the basis of many of its products, enabling the WWC to use consistent, objective, and transparent standards and procedures in its reviews, while also ensuring comprehensive coverage of the relevant literature. The WWC systematic review process consists of five steps: (1) Developing the review protocol; (2) Identifying relevant literature; (3) Screening studies; (4) Reviewing studies; and (5) Reporting on findings. In addition, the WWC reviews some studies outside of the systematic review process, such as those that receive significant media attention. These reviews are also guided by a review protocol and use the same WWC standards and reporting procedures. This "What Works Clearinghouse Standards Handbook, Version 4.1", provides a detailed description of the standards used by the WWC to review studies (step 4). Steps 1-3 and step 5 are described in a separate "What Works Clearinghouse Procedures Handbook" (ED602035). The substantive differences between this version of the standards (4.1) and the previous version (4.0) include the following: (1) The "pilot" designation for the single-case design (SCD) standards has been removed and additional clarification around standards elements has been added; (2) The language of "substantively important" has been removed; and (3) Small, nonsubstantive changes were made to clarify existing text. The remainder of the document is organized as follows. Chapter I provides a general introduction to the "Standards Handbook." Chapter II provides standards for randomized controlled trials and quasi-experimental designs. This chapter also provides additional standards for randomized controlled trials that present complier average causal effects, with supplemental technical detail in appendix D. Chapter III provides standards for studies that use regression discontinuity designs. Chapter IV illustrates standards for studies that use SCDs. Finally, chapter V provides information on outcome eligibility and confounding factors that applies broadly across designs. As the WWC continues to refine and develop standards, the "Standards Handbook" will be supplemented or revised to reflect these changes. [For version 4.0 of this guide, see ED577036.]