Background: : Congenital heart disease (CHD) is the major congenital anomalies, representing for one - third of all congenital anomalies and also leading cause of death in infants. Asia reported the highest CHD birth prevalence with 9.3 per 1,000 live births. Delayed diagnosis of congenital heart disease worsens preoperative condition and outcome of surgery in neonates, increased rates of cardiovascular compromise and end organ dysfunction the later CHD was recognized. Early detection of major congenital heart disease might improve the outcome of newborn babies Objective: : To determine the congenital heart disease (CHD) by pulse oximetry with clinical assessment screening in asymptomatic term neonates at Mother and Newborn Hospital in Vientiane Capital, Lao PDR. Methodology: : During the cross-sectional study, from July 1st, 2023 to August 30th, 2023 to investigate pulse oximetry with clinical assessment screening in newborn 24-72 hours of life at OPD nursery Unit, at Mother and Newborn Hospital in Vientiane Capital, Lao PDR from July 1st, 2023 to August 30th, 2023. Results: : A cross-sectional study involving 600 asymptomatic term newborn babies. The diagnosis congenital heart disease 11 of 600 cases (1.83%), 3 cases were critical congenital heart disease. Median age screening was 24 hours (ranged 24-72 hours) and the mean +/- SD was 31.80 +/- 11.18. Normal delivery was 80.5%. The median birth weight was 3000 grams (2100-4200). The gender was 50.3% female. Pulse oximetry with clinical assessment screening in positive was 1%, pulse oximetry alone was 0.5% and clinical assessment was 0.33%. Pulse oximetry with clinical assessment was detected 5 of 11 cases (45.45% sensitivity) of all congenital heart disease and 3 of 3 cases (100% sensitivity) of critical congenital heart disease, pulse oximetry alone was detected 3 of 11 cases (27.27% sensitivity) of all CHD and two of three cases (66.67% sensitivity) of critical CHD, clinical assessment alone was detected 2 of 11 cases (18.18% sensitivity) of all CHD and one of three cases (33.33% sensitivity) of critical CHD. The specificity of using pulse oximetry with clinical assessment was 99.83% for all CHD and 99.50% for critical CHD, pulse oximetry alone was 99.83% for both all CHD and critical CHD, and clinical assessment was 99.83% for all CHD and 99.50% for critical CHD. Conclusion: Pulse oximetry with clinical assessment screening is more effective at early detection of critical congenital heart disease in asymptomatic term newborns. It has good sensitivity and specificity for both critical and non- congenital heart diseases, including challenging cases that required urgent intervention. These findings suggest that pulse oximetry with clinical assessment screening should be used routinely to screen all newborns for congenital heart disease.