Nicotine dependence has been shown to hamper successful smoking cessation in adolescents. Nicotine dependence and depression are highly comorbid, but the relation between depression and smoking cessation is not yet fully understood. Therefore, the present study examines both the longitudinal reciprocal relation between nicotine dependence and depressive symptoms, and the longitudinal effect of these factors on successful smoking cessation and number of quit attempts. A 2-wave longitudinal study was conducted among 535 adolescents aged 1318. Written self-report questionnaires were administered in a classroom setting. Two models were tested, examining the mutual relation between nicotine dependence and depressive symptoms, as well as the predictive value of these factors on smoking cessation (n 535), and number of quit attempts (n 473) 1 year later. Adolescents with more depressive symptoms have significantly higher levels of nicotine dependence 1 year later. Higher levels of nicotine dependence negatively predicted subsequent successful smoking cessation, whereas depressive symptoms did not. In contrast, depressive symptoms predicted a higher number of unsuccessful quit attempts in the following year, whereas nicotine dependence did not. The findings suggest that adolescents tend to smoke cigarettes in order to diminish their depressive feelings, which might provide some support for the self-medication theory. Smoking cessation programs aiming at adolescents should not only focus on symptoms of nicotine dependence but should also pay attention to depressive feelings, since these feelings are related to a higher number of unsuccessful quit attempts.