Introduction: 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. Methods: 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. Results: 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. Conclusions: 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.