Many smokers report using e-cigarettes to help them quit smoking, but whether e-cigarettes aid cessation efforts is uncertain. To determine whether e-cigarette use after hospital discharge is associated with subsequent tobacco abstinence among smokers who plan to quit and are advised to use evidence-based treatment. Secondary data analysis of a randomized controlled trial. (ClinicalTrials.gov: NCT01714323 [parent trial]). 3 hospitals. 1357 hospitalized adult cigarette smokers who planned to stop smoking, received tobacco cessation counseling in the hospital, and were randomly assigned at discharge to a tobacco treatment recommendation (control) or free tobacco treatment (intervention). Self-reported e-cigarette use (exposure) was assessed 1 and 3 months after discharge; biochemically validated tobacco abstinence (outcome) was assessed 6 months after discharge. Twenty-eight percent of participants used an e-cigarette within 3 months after discharge. In an analysis of 237 propensity score-matched pairs, e-cigarette users were less likely than nonusers to abstain from tobacco use at 6 months (10.1% vs. 26.6%; risk difference, -16.5% [95% CI, -23.3% to -9.6%]). The association between e-cigarette use and quitting varied between intervention patients, who were given easy access to conventional treatment (7.7% vs. 29.8%; risk difference, -22.1% [CI, -32.3% to -11.9%]), and control patients, who received only treatment recommendations (12.0% vs. 24.1%; risk difference, -12.0% [CI, -21.2% to 2.9%]) (P for interaction= 0.143). Patients self-selected e-cigarette use. Unmeasured confounding is possible in an observational study. During 3 months after hospital discharge, more than a quarter of smokers attempting to quit used e-cigarettes, mostly to aid cessation, but few used them regularly. This pattern of use was associated with less tobacco abstinence at 6 months than among smokers who did not use e-cigarettes. Additional study is needed to determine whether regular use of e-cigarettes aids or hinders smoking cessation. National Heart, Lung, and Blood Institute.