Smoking-cessation follow-up care after hospitalization is known to be effective. Cost-effective and disseminable interventions adoptable by hospitals are needed.RCT.Fourteen hundred eighty-eight current smokers recruited during a tertiary care hospital stay were randomly assigned to Usual Care (UC) or Usual Care plus Web-Based Intervention (WI). Data were collected in 2011–2013 and analyzed in 2014–2015.UC provided brief bedside advice to quit, a quit plan template, and quitline contact information. WI included access to a website with asynchronous e-message communication with a tobacco counselor, use of interactive self-assessments, helpful cessation information, and access to additional web resources, as well as automated e-mail messages tailored for health concern and readiness to quit.Self-reported 30-day abstinence at 6 months was the primary outcome; a subset was verified by saliva cotinine.Six-month follow-up was completed by 83% of participants. No difference was found between study arms for self-reported abstinence rates in intent-to-treat (25.4% WI vs 26.8% UC) and complete case (31.3% WI vs 31.4% UC) analyses. Reduced smoking was reported by 45.5% (WI, n=276) and 47% (UC, n=296) of non-abstinent responders (p=0.59). Using a 10-ng/mL cotinine cut off, abstinence was verified in 52.1% of WI and 62.5% of UC (p=0.11). Significant covariates associated with abstinence at 6 months were being male, not smoking during hospitalization, being very confident in quitting, planning to quit/stay quit, smoking fewer days in the past 30 days, fewer years of smoking, and having cerebrovascular or connective tissue rheumatic disease as primary hospital diagnosis.Lack of difference between treatment arms suggests a strong effect for UC, WI was not effective, or both. Low intervention engagement may be partially responsible. Self-reported abstinence rates were relatively high in both arms, although the biochemically verified rates indicate over-reporting of abstinence. These findings suggest brief bedside counseling for all hospitalized smokers is beneficial.This study is registered at www.clinicaltrials.gov NCT01277250.