Although many cardiac lesions are diagnosed antenatally by fetal echocardiography, fatal critical congenital heart defects may still be missed. Objective: The purpose of this study is to evaluate the capability of pulse oximetry screening for early detection of critical congenital cardiovascular malformations in asymptomatic newborns. Methods: Pulse oximetry screening was performed on 118 asymptomatic newborns in the well infant nursery. Echocardiography examination was performed on all of the newborns included in the study. Data regarding true and false positives as well as negatives were collected and analyzed. Results: With oxygen saturation cut off of 94% pulse oximetry screening helped to diagnose 8 cases with critical congenital heart diseases while it failed to diagnose a case of Fallot tetralogy and another one with severe valvular pulmonary stenosis. This study revealed that best cut off value for preductal O2 saturation in relation to echocardiographic finding was 94% with standard error = 0.058 and 95% confidence interval = 0.718 – 0.869, and revealed that best cut off value for postductal O2 saturation in relation to echocardiographic finding was 92% with S.E = 0.051 and 95% C.I = 0.757 – 0.898. Conclusion: Study results showed that this screening test is simple, noninvasive, and inexpensive. The sensitivity, specificity, and predictive value in this population are satisfactory, indicating that screening should be applied to larger populations, particularly where lower rates of fetal detection are present and results in increased critical congenital heart diseases prevalence in asymptomatic newborns.