AIM: There are discrepancies in the reported prevalence of congenital heart disease (CHD). This study prospectively evaluated the prevalence of CHD in consecutive newborns using echocardiographic screening. METHODS: A cohort screening study was conducted in an unselected series of all live-birth newborns. Two-dimensional and colour Doppler echocardiography was performed at 0-4 days of life in 2067 consecutive neonates who were born at the Hamamatsu University Hospital, Japan, between May 2005 and April 2010. RESULTS: There were 104 cases of CHD in the 2067 live births. Ventricular septal defect and patent ductus arteriosus were the most frequent cardiac abnormalities. The prevalence of newborns with CHD who had signs or symptoms of CHD and/or required invasive intervention was 21.3 per 1000 live births. However, 60 patients (29.0 per 1000 live births) with CHD were asymptomatic and did not need invasive intervention. The overall prevalence of CHD in this series was 50.3 per 1000 live births. CONCLUSION: This prospective study using echocardiography for all newborns shows a higher prevalence of CHD than almost all of the previous studies.