OBJECTIVE: To investigate the efficacy of a cognitive-behavioral group intervention for children with chronic illnesses and to test the effect of an added parent component. METHODS: Children (n = 194) and their parents participated in a multicenter randomized clinical trial comparing a child-only intervention and a parent-child intervention to a wait-list control group. Primary outcomes were parent-and self-reported internalizing and externalizing problems; secondary outcomes were child disease-related coping skills (information seeking, relaxation, social competence, medical compliance, and positive thinking). Assessments took place at baseline and at 6- and 12-month follow-ups. Intention-to-treat mixed-model analyses were performed to test the difference in change in outcomes. RESULTS: The intervention had a positive effect on changes in parent-reported internalizing problems, child-reported externalizing problems, information seeking, social competence, and positive thinking. The additional effect of parental involvement was observed on parent-reported internalizing problems, child-reported externalizing problems, information seeking, and social competence. Illness severity and illness type did not moderate the effects. There were no intervention effects on child-reported internalizing problems, parent-reported externalizing problems, relaxation, or medical compliance. Of the families in the wait-list control group, 74% sought alternative psychological support during the intervention period. CONCLUSIONS: This RCT supports the efficacy of a protocol-based group intervention for children with chronic illnesses and their parents. Adding a parental component to the intervention contributed to the persistence of the effects. Future research should focus on moderating and mediating effects of the intervention. Copyright © 2013 by the American Academy of Pediatrics.