Objective: Scientific evidence implicates anxiety sensitivity (AS) as a risk factor for poor smoking cessation outcomes. Integrated smoking cessation programs that target AS may lead to improved smoking cessation outcomes, potentially through AS reduction. Yet, little work has evaluated the efficacy of integrated smoking cessation treatment on smoking abstinence. The present study prospectively examined treatment effects of a novel AS reduction-smoking cessation intervention relative to a standard smoking cessation intervention on smoking abstinence. Method: Participants (N = 529; 45.9% male; Mage = 38.23, SD = 13.56) included treatment-seeking smokers who received either a 4-session integrated anxiety-reduction and smoking cessation intervention (Smoking Treatment and Anxiety Management Program; [STAMP]) or a 4-session standard smoking cessation program (SCP). The primary aims focused on examining the effects of STAMP on (a) AS reduction during treatment, (b) early and late smoking point prevalence abstinence, and (c) the mechanistic function of AS reduction on treatment effects across early and late smoking abstinence. Results: Results indicated a significantly greater decline in AS in STAMP relative to SCP (B = −.72, p < .001). Treatment condition did not significantly directly predict early or late abstinence. However, the effect of STAMP on early abstinence was significantly mediated by reductions in AS (indirect = .16, 95% CI [.02, .40]). Conclusions: Findings provide evidence for the efficacy of a novel, integrated anxiety and smoking cessation treatment to reduce AS. Moreover, the meditation pathway from STAMP to early abstinence through reductions in AS suggest that AS is a clinically important mechanism of change for smoking cessation treatment and research.