Objectives: This study assessed the reliability and validity of the IMPACT-III questionnaire, a health-related quality of life (HRQoL) instrument, in French children with inflammatory bowel disease (IBD). Methods: Eighty-four children and adolescents (45 boys, aged 14.3 ± 2.7 years) were included in a validation study of the IMPACT-III questionnaire. Patients completed 2 questionnaires for measuring HRQoL: the IMPACT-III and the Pediatric Quality of Life Inventory 4.0 Generic Core Scale (PedsQL). Internal consistency was assessed using Cronbach α. Factor analysis was performed on data from the IMPACT-III to help construct domains. Concurrent validity was assessed by calculating Spearman correlation coefficients. Results: Cronbach α for the PedsQL total score was good (0.89). The most robust factor solution was a 3-domain structure: (a) Concerns, (b) Body Image and Physical Condition, and (c) Symptoms and Socializing. All domains had good reliability (0.674–0.863). Only 2 items had to be removed. Discriminant validity was demonstrated by significant differences ( P < 0.001) in median IMPACT-III scores between inactive and active disease for the total score (83.3 vs 72.0), and for Concerns ( P < 0.002) and Symptoms and Socializing ( P < 0.001). Conclusions: These results suggest that IMPACT-III appears to be a useful instrument for measuring HRQoL in French children with IBD.