Abstract: 　Objective　To find a reliable, simple, and easily-operated method for the screening of neonatal congenital heart disease (CHD). Methods　A total of 7 105 neonates born from January 2017 to July 2017 were selected. The validity and reliability of physical examination, pulse oximetry screening (POS), and perfusion index (PI) in the screening of neonatal CHD were evaluated according to the diagnosis made by color Doppler echocardiography. Results　When physical examination, POS or PI was used separately in screening for CHD, the sensitivities were in the range of 13.11%~73.77%, specificities 50.20%~99.34%, Youden indexes 0.12~0.70, the total coincidence rates 50.40%~98.86%, positive predictive values 1.27%~40.70%, and negative predictive values 99.29%~99.70%. When physical examination, POS and PI were combined (two or three indexes were positive) for screening, the sensitivities and Youden indexes were 85.25% and 0.82 respectively, which were higher than those of single indicators and suggested that the combination had higher authenticities. The total coincidence rate of the combination was 97.07%, and, although it was lower than POS group (98.86%) and PI screening group (98.58%), it still had a good reliability. Conclusions　The combination of physical examination, POS and PI has a certain clinical value in neonatal CHD screening.