This study examined whether e-cigarettes in appealing flavors enhance the decreases in cigarette smoking achieved by reducing the nicotine content of combusted cigarettes to minimally addictive levels (https://jamanetwork.com/journals/jamanetworkopen/article-abstract/2823300#google_vignette). In three Randomized Clinical Trials, decreases in cigarettes smoked daily achieved with reduced nicotine content cigarettes were significantly enhanced by providing adults from at-risk populations access to e-cigarettes in appealing flavors. These results suggest that a tobacco marketplace providing adult access to e-cigarettes in appealing flavors has potential to enhance the impact of a nicotine-reduction policy on cigarette smoking in populations with psychiatric conditions and socioeconomic disadvantage who are at greatest risk for smoking and associated adverse effects.