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Co-teaching encompasses students with and without disabilities who are taught by general and special educators in general education classrooms. However, other students with disabilities (SWD) may be taught in special education settings. The purpose of this meta-analysis is to compare academic achievement of SWD in co-taught versus special education classrooms. A search of published and gray literature rendered 26 eligible studies with a total of 3,714 SWD. Results indicated a moderate effect size (g = 0.47) of co-teaching. Further, eight moderators were considered to explore the role of contextual factors in SWD’s academic achievement. Although findings support that co-teaching improves student achievement, more information about SWD’s characteristics and effective instruction in each setting is needed.