This study aimed to report the progress and results of the newborn screening program for congenital heart disease (CHD) in south Shanghai between 2019 and 2023, and to evaluate the accuracy of the dual-index method (pulse oximetry (POX) plus cardiac murmur auscultation) in clinical practice. Between 2019 and 2023, a total of 198,606 (99.89%) newborns were screened for CHD, of whom 3299 (1.66%) tested positive, 3043 (92.24%) underwent echocardiography for CHD diagnosis and 1109 were diagnosed with CHD in a timely manner. Among 195,307 infants with negative screening results using the dual-index method, 139 (0.07%) were later diagnosed with CHD, and none of these infants died. More than half of these false-negative infants (59.39%) were identified due to the detection of a heart murmur during routine physical examinations within six months after birth. Compared to POX testing alone, the dual-index method significantly improved the sensitivity of screening for CHD, and kept high specificity in clinical practice. This study demonstrated that newborn screening for CHD has been well conducted in Shanghai, and the dual-index method had high accuracy and reliability for neonatal CHD screening in clinical practice.