Objective: More than one in three people worldwide are exposed to some form of childhood adversity (CA). CA is strongly associated with an increased risk for the development of mental health problems. Resilience factors (RFs), such as self-esteem, are known to reduce such vulnerability to mental health problems. Here we examine besides direct RF effects, whether RFs predominantly alter the relationship (i.e. moderation) or disrupt the developmental chain (i.e. mediation) between CA and mental health problems.Methods: We studied 1130 adolescents. CA exposure and 10 RFs (3 inter-individual e.g. friendships; 7 intra-individual e.g. self-esteem) were assessed at age 14. Mental health problems were assessed at age 14 and 17, and were combined into a mental distress index. We estimated direct-effect, moderation and mediation models.Results: When taking the effects of all 10 RFs into account, five of the 10 RFs had a significantly negative direct effect in the overall sample. However, of those five, only brooding revealed a significant effect in both the group of adolescents with and without CA. Of the 10 RFs, friendship support, family cohesion and distress tolerance had a significantly negative relationship with age-17 distress in the group of adolescents with CA, and no effect in the group of adolescents without CA. Yet, none of the three RFs revealed a significant moderation effect (p = 0.07-0.09). Positive self-esteem, negative self-esteem and aggression functioned as significant mediators for the relationship between CA and mental distress.Conclusions: In situations in which CA is not known, brooding seems to be the most beneficial RF, as it reduced subsequent mental distress in both adolescents with and without CA. Regarding RFs in the aftermath of CA, our findings provide predominant support for mediation rather than for moderation effects. More specifically, targeting negative self-esteem, positive self-esteem, and aggression seems most fruitful, when the aim is to disrupt the chain between CA and adolescent mental health problems.