Cigarette smoking is the leading preventable cause of death in the U.S. The U.S. Public Health Service Smoking Cessation Guideline recommends offering effective treatment that includes both medication and counseling to smokers in all health care settings, including hospitals. Nearly 4 million smokers are hospitalized each year, and hospital admission offers a “teachable moment” for intervention. In-hospital smoking cessation intervention is efficacious, but only if contact continues for more than 1 month after discharge. The challenge is to translate this efficacy research into clinical practice. Sustaining treatment after discharge is the major barrier to identifying a scalable, sustainable, cost-effective model for U.S. hospitals. Building on our prior work, this competitive renewal project compares the effectiveness of 2 innovative strategies that aim to sustain treatment after discharge. Both interventions are integrated into the electronic health record (EHR) and leverage technology to engage patients and streamline the delivery and uptake of evidence-based tobacco cessation treatment, but they differ in intensity and resources required. Specific Aim: To compare the effectiveness and cost-effectiveness of 2 interventions to increase hospitalized smokers’ long-term tobacco abstinence after discharge. Study Design: A multi-site randomized controlled comparative effectiveness trial will enroll 1350 adult smokers admitted to 3 hospitals in 3 states (MA, PA, and TN). All subjects will have a standardized in- hospital smoking intervention and be randomly assigned at discharge to Personalized Tobacco Care Management (PTCM) or Quitline eReferral (eReferral). PTCM, built on our prior work, offers smokers 4 weeks of free nicotine replacement therapy (NRT) in hand at discharge (refillable x 1) and 7 proactive automated contacts over 3 months via their preference of interactive voice response (IVR) phone calls or text messages. Each contact promotes cessation and offers access to a tobacco coach based in the health system who coordinates treatment with the smoker’s health care team via the EHR. eReferral is a less intensive, lower cost option in which smokers receive a one-time automated referral from the EHR to the state quitline at discharge. The quitline offers multi-session telephone counseling, 4 weeks of free mailed NRT, and sends a feedback report to the EHR. Outcomes, assessed at 1, 3, and 6 months after hospital discharge, are: (1) intervention effectiveness (biochemically-validated past 7-day tobacco abstinence at 6 month follow-up [1o outcome] and other tobacco abstinence measures); (2) smoking cessation treatment utilization, and (3) cost- effectiveness (incremental cost per quit). We will explore the interventions’ effects on hospital readmissions and mortality after discharge. Impact: New National Hospital Quality Measures (NHQM) adopted by Medicare and Medicaid programs include tobacco treatment measures, giving hospitals an incentive to ...