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Background: Despite the wealth of evidence regarding effective health behavior change techniques using digital interventions to focus on residents of high-income countries, there is limited information of a similar nature for low- and middle-income countries. Objective: The aim of this review is to identify and describe the available literature on effective social media–based behavior change interventions within low- and middle-income countries. Methods: This systematic review was conducted in accordance with the 2009 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. We searched PubMed, Embase, Elsevier, CINAHL, PsycInfo, and Global Index Medicus, and the final search was conducted on April 6, 2021. We excluded studies published before 2000 because of the subject matter. We included studies that evaluated interventions conducted at least partly on a social media platform. Results: We identified 1832 studies, of which 108 (5.89%) passed title-abstract review and were evaluated by full-text review. In all, 30.6% (33/108) were included in the final analysis. Although 22 studies concluded that the social media intervention was effective, only 13 quantified the level of social media engagement, of which, few used theory (n=8) or a conceptual model (n=5) of behavior change. Conclusions: We identified gaps in the settings of interventions, types and sectors of interventions, length of follow-up, evaluation techniques, use of theoretical and conceptual models, and discussions of the privacy implications of social media use. Trial Registration: PROSPERO CRD42020223572; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=223572

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Journal of Medical Internet Research