To determine the association between e-cigarette use and smoking cessation. We searched PubMed, Web of Science Core Collection, and EMBASE and computed the association of e-cigarette use with quitting cigarettes using random effects meta-analyses. We identified 64 papers (55 observational studies and 9 randomized clinical trials [RCTs]). In observational studies of all adult smokers (odds ratio [OR] = 0.947; 95% confidence interval [CI] = 0.772, 1.160) and smokers motivated to quit smoking (OR = 0.851; 95% CI = 0.684, 1.057), e-cigarette consumer product use was not associated with quitting. Daily e-cigarette use was associated with more quitting (OR = 1.529; 95% CI = 1.158, 2.019) and less-than-daily use was associated with less quitting (OR = 0.514; 95% CI = 0.402, 0.665). The RCTs that compared quitting among smokers who were provided e-cigarettes to smokers with conventional therapy found e-cigarette use was associated with more quitting (relative risk = 1.555; 95% CI = 1.173, 2.061). As consumer products, in observational studies, e-cigarettes were not associated with increased smoking cessation in the adult population. In RCTs, provision of free e-cigarettes as a therapeutic intervention was associated with increased smoking cessation. E-cigarettes should not be approved as consumer products but may warrant consideration as a prescription therapy.