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To examine the temporal relationship between stopping smoking and total mortality rates among middle-aged women.Prospective cohort study with 12 years of follow-up.Registered nurses residing in the United States.117 001 female registered nurses, ages 30 to 55 years, who were free of manifest coronary heart disease, stroke, and cancer (except nonmelanoma skin cancer) in 1976.Total mortality, further categorized into deaths from cardiovascular diseases, cancers, and violent deaths.A total of 2847 deaths (933 among “never smokers,” 799 among former smokers, and 1115 among current smokers) occurred during 1.37 million person-years of follow-up. The multivariate relative risks for total mortality compared with never smokers were 1.87 (95% CI, 1.65 to 2.13) for current smokers and 1.29 (CI, 1.14 to 1.46) for former smokers. Participants who started smoking before the age of 15 years had the highest risks for total mortality (multivariate relative risk, 3.15; CI, 2.16 to 4.59), cardiovascular disease mortality (relative risk, 9.94; CI, 5.15 to 19.19), and deaths from external causes of injury (relative risk, 5.39; CI, 1.84 to 15.78). Compared with continuing smokers, former smokers had a 24% reduction in risk for cardiovascular disease mortality within 2 years of quitting. The excess risks for total mortality and both cardiovascular disease and total cancer mortality among former smokers approached the level of that for never smokers after 10 to 14 years of abstinence. The health benefits of cessation were clearly present regardless of the age at starting and daily number of cigarettes smoked.The risk of cigarette smoking on total mortality among former smokers decreases nearly to that of never smokers 10 to 14 years after cessation.