In an ethnically-diverse, uninsured psychiatric sample with co-occurring drug/alcohol addiction, we evaluated the feasibility and reproducibility of a tobacco treatment intervention. The intervention previously demonstrated efficacy in insured psychiatric and nonpsychiatric samples with 20.0%-25.0% abstinence at 18 months.Daily smokers, recruited in 2009-2010 from psychiatric units at an urban public hospital, were randomized to usual care (on-unit nicotine replacement plus quit advice) or intervention, which added a Transtheoretical-model tailored, computer-assisted intervention, stage-matched manual, brief counseling, and 10-week post-hospitalization nicotine replacement.The sample (N = 100, 69% recruitment rate, age M = 40) was 56% racial/ethnic minority, 65% male, 79% unemployed, and 48% unstably housed, diagnosed with unipolar (54%) and bipolar (14%) depression and psychotic disorders (46%); 77% reported past-month illicit drug use. Prior to hospitalization, participants averaged 19 (SD = 11) cigarettes/day for 23 (SD = 13) years; 80% smoked within 30 minutes of awakening; 25% were preparing to quit. Encouraging and comparable to effects in the general population, 7-day point prevalence abstinence for intervention versus control was 12.5% versus 7.3% at 3 months, 17.5% versus 8.5% at 6 months, and 26.2% versus 16.7% at 12 months. Retention exceeded 80% over 12 months. The odds of abstinence increased over time, predicted by higher self-efficacy, greater perceived social status, and diagnosis of psychotic disorder compared to unipolar depression.Findings indicate uninsured smokers with serious mental illness can engage in tobacco treatment research with quit rates comparable to the general population. A larger investigation is warranted. Inclusion of diverse smokers with mental illness in clinical trials is supported and encouraged.