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Background: The natural course of onset of cigarette use has been conceptualized as progressing sequentially through 5 stages (preparation, trying, irregular use, regular use, nicotine-dependent smoking). However, recent studies suggest that symptoms of nicotine dependence can occur early in the onset process, raising questions about the validity of this model. The objective of our study was to describe the sequence and timing of 12 milestones (6 related to cigarette use and 6 to symptoms of nicotine dependence) during onset of cigarette use. Methods: Grade 7 students in 10 secondary schools in Montréal (n= 1293) were followed prospectively every 3-4 months for 5 years. Using Kaplan--Meier analysis, we computed the number of months after first puff at which the cumulative probability of attaining each milestone was 25%, among 311 participants who initiated cigarette use during follow-up. Results: Inhalation rapidly followed first puff. The cumulative probability of inhalation was 25% at 1.5 months (95% confidence interval [CI] 1.5-2.5). The cumulative probability (and 95% CI) was 2.5 months (1.5-2.5) for mental addiction, 2.5 (1.0-3.0) for smoking a whole cigarette, 4.5 (2.5-8.8) for cravings, 5.4 (3.8-9.7) for physical addiction, 8.8 (7.0-11.9) for monthly smoking, 11.0 (6.4-16.8) for withdrawal symptoms, 13.0 (10.3-20.5) for tolerance, 19.4 (14.5-31.7) for weekly smoking, 19.5 (14.0-23.9) for lifetime total of 100 cigarettes, 23.1 (19.7-37.6) for daily smoking and 40.6 (35.1-56.0) for conversion to tobacco dependence. Interpretation: Symptoms of nicotine dependence develop soon after first puff and can precede monthly, weekly and daily smoking. Cessation interventions that manage dependence symptoms may be needed soon after first puff. [ABSTRACT FROM AUTHOR]