OBJECTIVE Neurodevelopmental impairment and impaired quality of life constitute a major source of morbidity among children with complex congenital heart disease (CHD), in particular for single ventricle morphologies. Risk factors and quality of life determining clinical and neurodevelopmental outcome at two years of age are examined. METHODS In a two-center cohort study, 48 patients with SV-morphology (26 HLHS, 22 other types of univentricular heart defect) have been examined prior Fontan procedure between 2010 and 2015. Patients were assessed with the Bayley Scales of Infant and Toddler Development III (Bayley-III) and the Preschool Children Quality of Life Questionnaire (TAPQOL). RESULTS 44 patients received Hybrid (n=25), Norwood procedure (n=7), or shunt or banding procedure (n=12) as first surgery before subsequent bidirectional cavopulmonary anastomosis (n=48). Median cognitive, language, and motor composite scores on the Bayley-III were 100 (range 65-120), 97 (68-124), and 97 (55-124), respectively. Language composite score was significantly below the norm (p=0.025), Risk factors for poorer neurodevelopmental outcome were prolonged mechanical ventilation, longer days of hospital stay, and more reinterventions (all p<0.05). Parents reported a good quality of life for their children. CONCLUSIONS Children undergoing Fontan procedure show a favorable development and good quality of life. More complicated postoperative course and reinterventions constitute risk factors for impaired neurodevelopment. Improving postoperative management and implementing routine follow-up assessments are measures to further improve the neurodevelopmental outcome of this high-risk patient population.