Objective: Prevailing theory and research suggests the psychological and physiological discomfort associated with tobacco withdrawal may play a formative role in the risk of cessation failure. Yet, research elucidating cognitive-affective vulnerability characteristics that contribute to increased tobacco withdrawal severity during periods of planned abstinence is highly limited. In the current study, we explored whether smokers with greater reductions of Anxiety Sensitivity (AS) and dysphoria during a smoking cessation intervention would experience less severe postquit tobacco withdrawal. Method: Specifically, the interactive effect of change (from preintervention baseline to quit day) in AS and dysphoria in relation to postquit withdrawal severity (quit day through 12 weeks postquit) was examined among treatment-seeking adult smokers enrolled in a smoking cessation trial (N = 198; 55.3% female; 86.8% Caucasian; Mage = 38.8, SD = 14.0). Results: Results indicated that the interactive effect of change in AS and dysphoria was related to linear change in postquit withdrawal symptoms. Specifically, larger reductions in AS were associated with a faster decline in the severity of withdrawal symptoms across the 12-week postquit period only for individuals with lower (but not higher) reductions in dysphoria. Additionally, the findings indicated that reducing levels of AS and dysphoria prequit is broadly related to the degree of change in postquit withdrawal symptoms. Conclusion: Collectively, these data suggest there is apt to be clinical merit to employing strategies to address AS and/or dysphoria to more effectively manage emergent withdrawal symptoms following smoking cessation treatment.