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Objectives: Some people who stop smoking experience improved mood, but few studies have examined this relationship after hospitalization or accounted for concomitant substance use and psychological factors. We examined associations between smoking abstinence after a hospital discharge and change in depression and anxiety symptoms., Methods: We conducted a secondary analysis of data from the Helping HAND 4 smoking cessation trial, which enrolled people who used tobacco when admitted to three academic medical center general hospitals. Participants (n = 986) were categorized as continuously abstinent (CA) or not. We used linear and logistic regression to model continuous and binary measures of depression (Patient Health Questionnaire [PHQ-8] ≥/<10), and anxiety (Generalized Anxiety Disorder Assessment [GAD-7], ≥/<8) over 6 months, adjusting for baseline mood, psychological factors, and substance use. Binary outcomes were defined using established clinical thresholds to aid in the clinical interpretation of the results., Results: Mean age was 52.3 years, 56.5% were female, and the baseline mean cigarettes/day was 16.2 (SD: 3.2). In the adjusted analyses, depression and anxiety scores improved more in CA than non-CA participants over 6 months (difference-in-improvement, 2.43 [95% CI: 1.50-3.36] for PHQ-8; 3.04 [95% CI: 2.16-3.93] for GAD-7). At 6 months, CA participants were more likely to have a PHQ-8 score <10 (aOR = 2.07 [95% CI: 1.36-3.16]) and a GAD-7 score <8 (aOR = 2.90 [95% CI: 1.91-4.39])., Conclusions: Individuals who were CA, compared to those who were not, had fewer depression and anxiety symptoms at 6 months, and were twice as likely to score below the population screening thresholds for major depression and anxiety disorders. Clinicians should emphasize the association between continuous abstinence and improved mood symptoms after hospital discharge., Competing Interests: Conflicts of interests: Dr. Rigotti reported receiving personal fees from Achieve Life Sciences, UpToDate (Wolters Kluwer), and grants from Achieve Life Sciences outside the submitted work. Dr. Tindle reported serving as a PI of studies funded by the National Institutes of Health in which smoking cessation medications were donated by the manufacturer and as an unpaid consultant for Achieve Life Sciences., (Copyright © 2024 American Society of Addiction Medicine.)