Introduction: Pulse oximetry screening (POS) in the newborn period has been shown to improve early detection of critical congenital heart disease (CCHD) before significant morbidity and/or mortality develop. Acceptable sea-level saturation thresholds range from 90-95% in newborns whereas at altitudes >1500m this decreases to 88-93% due to lower partial pressures of oxygen. Objective: To determine whether lower oxygen saturation thresholds would be better suited to direct POS in neonates born at altitude (>1500m), and to compare the revised cut-offs to those recommended by the American Academy of Pediatrics (AAP) guidelines for POS for CCHD. Methods: We performed a prospective descriptive study of well newborn patients born during a period of two months (October and November 2015) at Chris Hani Baragwanath Academic Hospital (CHBAH). POS was conducted in term newborns at >12 hours of age measuring saturations in the right hand (pre-ductal) and either foot (post-ductal). Using a modified version of the AAP POS guidelines (Pre-ductal saturations 93% and post-ductal 88% for CHBAH versus 95%/90% for AAP), all patients underwent echocardiogram to confirm the results of screening. Results were analysed assessing the effects of altitude on screening. Results: Three-hundred and forty eight infants were included in the study. No patients with CCHD were identified. Mean saturations were 94% for right hand and foot. Adjusted cut-offs of 93-88% result in 15.2% of patients requiring repeat screening and 41.3% using AAP guidelines (95-90%). Failed screens were attributed to physiological right-to-left or bi-directional shunting in 3/348 (0.8%). Accuracy is comparable internationally (sensitivity (100%), specificity (99.4%) and false positive rate (0.64%)). Conclusions: Altitude does not affect the accuracy of POS. If screening is to be implemented above 1700m, adjusted POS cut-offs of 93-88% should be considered at altitudes above 1700m.LG201