Background: This study aims to assess sex differences with regards to outcome, cardiovascular dimensions, and functional capacity in patients with a Fontan circulation. Methods: In this single-center prospective, standardised cohort study of 60 Fontan patients (30 females, 50%) aged ≥10 years, the association between sex and the combined outcome variable of all-cause mortality, heart/heart-lung transplantation (including listing) and Fontan-related hospitalisation was investigated. Secondary outcome measures included functional capacity and ventricular dimensions, measured by cardiac magnetic resonance imaging (CMR), cardiopulmonary exercise testing (CPET) and concomitant clinical assessment. Results: Baseline characteristics including age, diagnosis and surgical history did not differ between female and male patients. During a median follow-up time of 5.75 (5.4–6.0) years, the combined outcome variable occurred in 17 (28%) patients. Female Fontan patients had 13 (43%) adverse events and males 4 (13%). Event-free survival differed significantly (p = 0.040). At baseline, the majority of males was in NYHA class I (n = 19, 63%), whereas the majority of females was in NYHA class II or III (n = 20, 67%) (p = 0.036). Male Fontan patients had about 25% higher end-diastolic volume (p = 0.001) indexed for body surface area (BSA), 28% higher indexed end-systolic volume (p = 0.004) and 25% more indexed ventricular mass (p