BACKGROUND: Despite a lack of empirical evidence, many smokers and health professionals believe that tobacco smoking reduces anxiety, which may deter smoking cessation. AIMS: The study aim was to assess whether successful smoking cessation or relapse to smoking after a quit attempt are associated with changes in anxiety. METHOD: A total of 491 smokers attending National Health Service smoking cessation clinics in England were followed up 6 months after enrolment in a trial of pharmacogenetic tailoring of nicotine replacement therapy (ISRCTN14352545). RESULTS: There was a points difference of 11.8 (95% CI 7.7-16.0) in anxiety score 6 months after cessation between people who relapsed to smoking and people who attained abstinence. This reflected a three-point increase in anxiety from baseline for participants who relapsed and a nine-point decrease for participants who abstained. The increase in anxiety in those who relapsed was largest for those with a current diagnosis of psychiatric disorder and whose main reason for smoking was to cope with stress. The decrease in anxiety on abstinence was larger for these groups also. CONCLUSIONS: People who achieve abstinence experience a marked reduction in anxiety whereas those who fail to quit experience a modest increase in the long term. These data contradict the assumption that smoking is a stress reliever, but suggest that failure of a quit attempt may generate anxiety.