Introduction: Anxiety sensitivity (AS), defined as the extent to which individuals believe anxiety and internal sensations have harmful consequences, is associated with the maintenance and relapse of smoking. Yet, little is known about how AS interplays with negative affect during the quit process in terms of smoking behavior. To address this gap, the current study examined the dynamic interplay between AS, negative affect, and smoking lapse behavior during the course of a self-guided (unaided) quit attempt. Methods: Fifty-four participants (33.3% female; M_age = 34.6, SD = 13.8) completed ecological momentary assessment procedures, reporting on negative affect and smoking status via a handheld computer device, three times per day for the initial 14 days of the self-guided cessation attempt. Results: As expected, a significant interaction was observed, such that participants characterized by high levels of AS were at a higher risk of smoking on days when negative affect was high (relative to low). Results also revealed a significant interaction between AS and daily smoking lapse behavior in terms of daily change in negative affect. Participants characterized by high levels of AS reported significant increases in same-day negative affect on days when they endorsed smoking relative to days they endorsed abstinence. Conclusions: This study provides novel information about the nature of AS, negative affect, and smoking behavior during a quit attempt. Results suggest there is a need for specialized intervention strategies to enhance smoking outcome among this high-risk group that will meet their unique "affective needs." Implications: The current study underscores the importance of developing specialized smoking cessation interventions for smokers with emotional vulnerabilities.