To examine the benefits of a culturally targeted compared with a nontargeted smoking cessation intervention on smoking cessation outcomes among lesbian, gay, bisexual, and transgender (LGBT) smokers. A prospective randomized design was used to evaluate the added benefits of an LGBT culturally targeted Courage to Quit (CTQ-CT) smoking cessation treatment (N = 172) compared with the standard intervention (CTQ; N = 173). The smoking cessation program consisted of six treatment sessions combined with 8 weeks of nicotine replacement therapy. The primary smoking cessation outcome was 7-day point prevalence quit rates. Secondary outcomes examined included changes in nicotine dependence, nicotine withdrawal, cigarettes per day, smoking urges, self-efficacy, and readiness to quit. Overall quit rates were 31.9% at 1 month, 21.1% at 3 months, 25.8% at 6 months, and 22.3% at 12 months. Quit rates did not differ between treatment groups 1 month OR = 0.81 (0.32, 2.09), 3 months OR = 0.65 (0.23, 1.78), 6 months OR = 0.45 (0.17, 1.21), 12 months OR = 0.70 (0.26, 1.91). Compared with baseline levels, all secondary smoking cessation outcomes measured were improved at 1 month and were maintained at 12-month follow-up. Compared with the CTQ, the CTQ-CT intervention was more highly rated on program effectiveness (d = 0.2, p = .011), intervention techniques (d = 0.2, p = .014), the treatment manual (d = 0.3, p < .001), and being targeted to the needs of LGBT smokers (d = 0.5, p < .0001). LGBT smokers receiving the CTQ intervention achieved smoking cessation outcomes in the range reported for other demographic groups. Cultural targeting improved the acceptability of the intervention but did not confer any additional benefit for smoking cessation outcomes. Study results have implications for understanding the benefits of culturally targeted compared with nontargeted smoking cessation interventions for improving smoking cessation outcomes among LGBT smokers. Shorter and longer term 7-day point prevalence quit rates associated with the targeted and nontargeted interventions were modest but comparable with other group-based interventions delivered in a community setting. Although cultural targeting improved the overall acceptability of the intervention, no added benefits were observed for the culturally targeted intervention on either the primary or secondary outcomes.