Background: Congenital heart disease is a significant morbidity and determinant of mortality in persons with Down syndrome, the most prevalent human chromosomal anomaly. Yet, dearth of literature persists about its spectrum in Nigerian children. Objective: To determine the spectrum and outcome of congenital heart disease among children with Down syndrome in the Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria. Methods: A prospective study of all children diagnosed with Down syndrome seen over a 21 month period. Data obtained and analysed included age, sex, parental ages, birth order, anthropometry, echocardiography diagnoses, complications, treatments and outcomes. Results: Of the 70 children with Down syndrome, 53 (75.7%) had congenital heart disease of which 24 (45.3%) had solitary lesions with atrio-ventricular canal defect being the most common while 29 (54.7%) had multiple lesions of which the combination of ventricular septal defect with atrial septal defect was the most common. However, when all individual lesions were summed together, the most prevalent was atrial septal defect. The mean maternal and paternal ages were 31.4 and 41.2 years respectively. Over half were 1st or 2nd born. Higher proportion of those with congenital heart disease than those without were undernourished (67.9% versus 35.3%; p=0.035). Only 4 (7.5%) have had definitive corrective interventions, 26.4% developed pulmonary arterial hypertension and 18.9% had left ventricular dysfunction. Conclusion: The occurrence of congenital heart disease in these Nigerian children with Down syndrome is high the pattern being comparable with that in the literature with atrio-ventricular canal defect and other septal defects being most common. Presentation is late and the level of definitive care is poor. Routine and early cardiologic evaluation of all children suspected with Down syndrome is advocated.