ABSTRACT: BACKGROUND:Previous reviews of rural physical activity interventions were focused on intervention effectiveness and had reported overall mixed findings. The purpose of this systematic review was to apply the Reach, Efficacy, Adoption, Implementation and Maintenance (RE-AIM) framework to evaluate the extent to which rural physical activity interventions in the U.S. have reported on dimensions of internal and external validity and to offer suggestions for future physical activity interventions for rural U.S. POPULATIONS: METHODS:Pubmed, PsychINFO, CINAHL, PAIS, and Web of Science were searched through February 2019 to identify physical activity intervention studies conducted in rural regions in the U.S. with adult populations. Titles, abstracts, and full texts of articles were reviewed against inclusion and exclusion criteria. Data extraction from included articles included a summary of study details, rural classification system used, and the presence or absence of a total 61 RE-AIM indicators, including reach (n?=?13), efficacy/effectiveness (n?=?10), adoption (n?=?21), implementation (n?=?9), and maintenance (n?=?8). RESULTS:A total of 40 full-text articles representing 29 unique studies were included. Classifications of rurality included self-statements by authors (n?=?19, 65.5%), population/census-based definitions (n?=?3, 10.3%), Rural Urban Continuum Codes (n?=?3, 10.3%), Rural Urban Commuting Area codes (n?=?2, 6.9%), the 2014 Alabama Rural Health Association classification system (n?=?1, 3.4%) and the U.S. Office of Management and Budget classification system (n?=?1, 3.4%). Individual studies reported between 14.8 to 52.5% of total RE-AIM indicators. Studies reported 15.4 to 84.6% indicators for reach; 20.0 to 70.0% indicators for efficacy/effectiveness; 4.8 to 47.6% indicators for adoption; 11.1 to 88.9% indicators for implementation; and 0 to 25.0% indicators for maintenance. CONCLUSIONS:We found an overall poor reporting of components related to external validity, which hinders the generalizability of intervention findings, and a lack of consistency in the definition of rurality. Future research should focus on balancing factors of internal and external validity, and should aim to develop a greater understanding of how rurality influences health and behavior to provide contextual knowledge needed to advance the translation of physical activity interventions into practice in rural communities and reduce rural health disparities. TRIAL REGISTRATION:The review protocol was registered with PROSPERO: CRD42019116308.