Introduction: This study tested the efficacy of group-based culturally specific cognitive behavioral therapy (CBT) for smoking cessation among low-income African Americans. Methods: Participants (N = 342; 63.8% male; M = 49.5 years old; M cigarettes per day = 18) were randomly assigned to eight sessions of group-based culturally specific or standard CBT, plus 8 weeks of transdermal nicotine patches. Biochemically verified 7-day point prevalence abstinence (ppa) was assessed at the end-of-therapy (ie, CBT) (EOT), and 3-, 6-, and 12-month follow-ups. Primary outcomes were the longitudinal intervention effect over the 12-month follow-up period, and 7-day ppa at the 6-month follow-up. Secondary outcomes included 7-day ppa at the EOT and 12-month follow-up, and intervention ratings. Generalized linear mixed modeling tested the longitudinal effect and logistic regression tested effects at specific timepoints. Results: Generalized linear mixed modeling demonstrated a longitudinal effect of intervention condition. Specifically, 7-day ppa was two times (P = .02) greater following culturally specific CBT versus standard CBT when tested across all timepoints. Analyses by timepoint found no significant difference at 6 or 12 months, yet culturally specific CBT was efficacious at the EOT (62.5% vs. 51.5% abstinence, P = .05) and the 3-month follow-up (36.4% vs. 22.9% abstinence, P = .007). Finally, intervention ratings in both conditions were high, with no significant differences. Conclusions: Culturally specific CBT had a positive longitudinal effect on smoking cessation compared to a standard approach; however, the effects were driven by short-term successes. We recommend the use of group-based culturally specific CBT in this population when possible, and future research on methods to prevent long-term relapse. Implications: Culturally specific interventions are one approach to address smoking-related health disparities; however, evidence for their efficacy in African Americans is equivocal. Moreover, the methodological limitations of the existing literature preclude an answer to this fundamental question. We found a positive longitudinal effect of culturally specific CBT versus standard CBT for smoking cessation across the follow-up period. Analyses by assessment point revealed that the overall effect was driven by early successes. Best practices for treating tobacco use in this population should attend to ethnocultural factors, but when this is not possible, standard CBT is an alternative approach for facilitating long-term abstinence.