Objective: First, to compare QOL and illness perceptions between patients with a Fontan circulation and patients with anatomically simple defects (ie, atrial septal defects [ASD] or ventricular septal defects [VSD]). Second, to explore illness perceptions as a mediator of the association between congenital heart disease (CHD) diagnosis and QOL. Design: Cross-sectional observational study. Setting: Twenty-four cardiology centers from 15 countries across five continents. Patients: Four hundred thirty-five adult patients with congenital heart disease (177 Fontan and 258 ASD/VSD) ages 18-83 years. Outcome Measures: QOL and illness perceptions were assessed by the Satisfaction With Life Scale and the Brief Illness Perceptions Questionnaire, respectively. Results: Patients with a Fontan circulation reported lower QOL (Wald Z = −3.59, p =