Tobacco withdrawal symptoms have been shown to play a significant role in mediating relapse to smoking in adult smokers; however, few prospective studies have examined the course of tobacco withdrawal symptoms over time and their connection to lapse in adolescent smokers. Withdrawal symptoms were assessed weekly for 4 weeks in a sample of adolescent smokers participating in a pilot cessation intervention. Adolescent smokers experienced an exacerbation in overall withdrawal symptoms, particularly of cravings and restlessness, although symptoms were generally mild. The course of symptoms was different for boys and girls: Girls generally experienced a peak and subsequent decline in symptoms early in the establishment of abstinence, whereas boys experienced a constant level of symptoms that did not decline over the 4 weeks. Finally, withdrawal symptoms experienced on quit day were not related to lapse to smoking during the course of treatment for either boys or girls. These results suggest that although withdrawal symptoms may be uncomfortable, they may not be the most salient to a lapse to smoking for adolescent smokers attempting to quit. These findings have direct implications for the design and implementation of treatment of nicotine dependence in adolescent smokers.