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Background: Disease prevention is a central aspect of primary care practice and is comprised of primary (eg, vaccinations), secondary (eg, screenings), tertiary (eg, chronic condition monitoring), and quaternary (eg, prevention of overmedicalization) levels. Despite rapid digital transformation of primary care practices, digital health interventions (DHIs) in preventive care have yet to be systematically evaluated., Objective: This review aimed to identify and describe the scope and use of current DHIs for preventive care in primary care settings., Methods: A scoping review to identify literature published from 2014 to 2020 was conducted across multiple databases using keywords and Medical Subject Headings terms covering primary care professionals, prevention and care management, and digital health. A subgroup analysis identified relevant studies conducted in US primary care settings, excluding DHIs that use the electronic health record (EHR) as a retrospective data capture tool. Technology descriptions, outcomes (eg, health care performance and implementation science), and study quality as per Oxford levels of evidence were abstracted., Results: The search yielded 5274 citations, of which 1060 full-text articles were identified. Following a subgroup analysis, 241 articles met the inclusion criteria. Studies primarily examined DHIs among health information technologies, including EHRs (166/241, 68.9%), clinical decision support (88/241, 36.5%), telehealth (88/241, 36.5%), and multiple technologies (154/241, 63.9%). DHIs were predominantly used for tertiary prevention (131/241, 54.4%). Of the core primary care functions, comprehensiveness was addressed most frequently (213/241, 88.4%). DHI users were providers (205/241, 85.1%), patients (111/241, 46.1%), or multiple types (89/241, 36.9%). Reported outcomes were primarily clinical (179/241, 70.1%), and statistically significant improvements were common (192/241, 79.7%). Results were summarized across the following 5 topics for the most novel/distinct DHIs: population-centered, patient-centered, care access expansion, panel-centered (dashboarding), and application-driven DHIs. The quality of the included studies was moderate to low., Conclusions: Preventive DHIs in primary care settings demonstrated meaningful improvements in both clinical and nonclinical outcomes, and across user types; however, adoption and implementation in the US were limited primarily to EHR platforms, and users were mainly clinicians receiving alerts regarding care management for their patients. Evaluations of negative results, effects on health disparities, and many other gaps remain to be explored., (©Van C Willis, Kelly Jean Thomas Craig, Yalda Jabbarpour, Elisabeth L Scheufele, Yull E Arriaga, Monica Ajinkya, Kyu B Rhee, Andrew Bazemore. Originally published in JMIR Medical Informatics (https://medinform.jmir.org), 21.01.2022.)