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Objectives: Because US smoking rates have not declined during the past decade, there is a renewed need to identify factors associated with smoking cessation. Using a nested case-control design, we explored the association between ability to sustain cessation over an extended period and demographic, smoking, medical, and behavioral variables., Methods: We selected a sample of 1379 sustained quitters (abstinent from smoking for at least 40 months) and 1388 relapsers (abstinent for more than 8 months before relapse) from participants in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study, a nutritional intervention study involving Finnish men aged 50 to 69 years at baseline. Contingency table and multiple regression analyses were used to evaluate potential differences between the 2 groups on baseline variables., Results: Compared with sustained quitters, relapsers were more likely to report symptoms of emotional distress and higher levels of nicotine dependence, to drink more alcohol, and to report more medical conditions., Conclusions: Factors associated with both tobacco use and comorbid conditions impact an individual's ability to maintain long-term smoking cessation. Understanding the underlying mechanisms of action and potential common pathways among these factors may help to improve smoking cessation therapies.