Depression is a serious disturbance, which may have negative consequences in various areas of adolescents' life, namely in academic achievement [10]. On the contrary, well-being in adolescence is associated with lower levels of depressive symptoms and better integration in school [9]. In the present study, we intend to analyze the relationships between subjective well-being, sociodemographic variables, academic performance and depression, as well as the relation between depressive symptomatology and academic achievement. Additionally, the relation of negative life events with the subjective well-being of adolescents was studied. Moreover, the moderating effect of negative life events in the relation between subjective well-being and depressive symptomatology was analyzed. The participants were 319 adolescents (217 girls and 102 boys) aged between 13 and 15 years old, attending 8th and 9th grade in public schools, who participated in a Portuguese study about prevention of adolescent depression. Depressive symptoms were assessed by the Child Depression Inventory (CDI; Kovacs [25]; Negative life events were evaluated by the Daily Hassles Microsystem Scale (DHMS; Seidman, et al.,[30]; Subjective well-being was measured by the Mental Health Continuum Short Form (MHC-SF; Keyes [28]). Results revealed the existence of statistically significant gender differences in the three factors of wellbeing (emotional, psychological and social well-being). Additionally, we found that adolescents with higher levels of depressive symptoms and negative life events show poor school performance. On the contrary, adolescents with higher level of subjective well-being report higher academic performance. The present study also revealed the existence of negative associations between negative life events and subjective well-being. Finally, this research showed that subjective well-being and negative life events were significant predictors of depression and that negative life events were significant moderators between well-being and depressive symptoms. In general, the results are in agreement with previous studies and have important implications for the development of depression prevention programs in adolescence and for the improvement of academic achievement.