BACKGROUND: Individuals with serious mental illness (SMI) smoke at disproportionately higher rates than those without SMI. We demonstrated, in a randomized controlled trial (RCT) of 342 adult smokers receiving inpatient psychiatric care, that an in-person, motivational interviewing (MI)-based, Sustained Care (SusC) intervention vs. Usual Care (UC) resulted in significantly higher rates of confirmed smoking abstinence at 6-months post-hospital discharge and significantly increased smoking cessation treatment utilization. While successful, this SusC intervention would be challenging to implement broadly in psychiatric hospitals. The current efficacy trial will develop and test an MI-based Sustained Care intervention delivered as a mobile app for iPad and will determine whether this approach can produce higher cessation rates compared to usual care for smokers admitted to a psychiatric inpatient unit. METHODS: A total of 250 eligible patients hospitalized for psychiatric illness will be randomized to: Tablet-delivered Sustained Care (T-SusC) or Usual Care (UC), and will be followed for six months after discharge. Participants assigned to UC will receive brief, in-hospital tobacco education. Those assigned to T-SusC will receive the brief tobacco education, plus a 40-min, in-hospital MI intervention delivered via a mobile application (app) for iPad use. They will also receive up to 8 weeks of free nicotine patches and a referral to the Texas Tobacco Quitline. Smoking cessation outcomes will be measured at 1-, 3- and 6-months post hospital discharge. CONCLUSION: Results from this efficacy trial may add to our understanding of acceptable and effective smoking cessation approaches for patients hospitalized with SMI.