ABSTRACT: To assess the potential benefit of digital health interventions (DHIs) on cardiovascular disease (CVD) outcomes (CVD events, all-cause mortality, hospitalizations) and risk factors compared with non-DHIs.We conducted a systematic search of PubMed, MEDLINE, EMBASE, Web of Science, Ovid, CINHAL, ERIC, PsychINFO, Cochrane, and Cochrane Central Register of Controlled Trials for articles published from January 1, 1990, through January 21, 2014. Included studies examined any element of DHI (telemedicine, Web-based strategies, e-mail, mobile phones, mobile applications, text messaging, and monitoring sensors) and CVD outcomes or risk factors. Two reviewers independently evaluated study quality utilizing a modified version of the Cochrane Collaboration risk assessment tool. Authors extracted CVD outcomes and risk factors for CVD such as weight, body mass index, blood pressure, and lipid levels from 51 full-text articles that met validity and inclusion criteria.Digital health interventions significantly reduced CVD outcomes (relative risk, 0.61; 95% CI, 0.46-0.80; P<.001; I(2)=22%). Concomitant reductions in weight (-2.77 lb [95% CI, -4.49 to -1.05 lb]; P<.002; I(2)=97%) and body mass index (-0.17 kg/m(2) [95% CI, -0.32 kg/m(2) to -0.01 kg/m(2)]; P=.03; I(2)=97%) but not blood pressure (-1.18 mm Hg [95% CI, -2.93 mm Hg to 0.57 mm Hg]; P=.19; I(2)=100%) were found in these DHI trials compared with usual care. In the 6 studies reporting Framingham risk score, 10-year risk percentages were also significantly improved (-1.24%; 95% CI, -1.73% to -0.76%; P<.001; I(2)=94%). Results were limited by heterogeneity not fully explained by study population (primary or secondary prevention) or DHI modality.Overall, these aggregations of data provide evidence that DHIs can reduce CVD outcomes and have a positive impact on risk factors for CVD.