Background: The aim of this study was to assess the role of protective factors as mediators and/or moderators of the relationship between coexisting emotional and conduct problems and quality of life (QoL) among adolescents with attention-deficit/hyperactivity disorder (ADHD). Methods: The sample consisted of 194 adolescents with ADHD. Participants completed measures of individual competencies, family cohesion and social support, and QoL. Coexisting emotional and conduct problems were assessed using the Strength and Difficulties Questionnaire. Results: Individual competencies and social support mediated the association between emotional and conduct problems and QoL. Family cohesion was associated with both emotional and conduct problems. No moderating effects of protective factors and coexisting problems were found. Conclusions: The assessment of individual competencies, social resources, and family cohesion may identify potential treatment goals for adolescents with ADHD and coexisting problems, and may contribute to improvements in QoL.