Purpose: The aim of this study was to examine the association of negative life events and parent-adolescent attachment relationship quality with mental health problems and to explore an interaction between the parent-adolescent attachment relationship and one or multiple negative life events on the mental health of adolescents. Methods: A two-year longitudinal study was conducted among first-year secondary school students (N = 3181). The occurrence of life events and the quality of parent-adolescent attachment were assessed at baseline and mental health status at two-year follow-up by means of self-report questionnaires. Binary logistic regression analyses were conducted to assess associations between life events, parent-adolescent attachment and mental health problems. Relative Excess Risk due to Interaction techniques were used to determine the interaction effects on the additive scale. Results: Life events were related to mental health status, as was parent-adolescent attachment. The combined effect of an unfavourable parent-adolescent attachment with life events on mental health was larger than the sum of the two individual effects. Among adolescents with one life event or multiple life events, an unfavourable parent-adolescent attachment increased the risk of mental health problems at follow-up compared to the group without life events. Conclusion: Results supported an interaction effect between parent-adolescent attachment and negative life events on mental health. Especially adolescents with one or multiple life events and an unfavourable parent-adolescent attachment seems to be a vulnerable group for mental health problems. Implications for further research are discussed.