Background & Aims The dilemma of early diagnosis of biliary Atresia (BA), particularly distinguishing it from other causes of neonatal cholestasis is challenging. The aim was to design and validate a scoring system for early discrimination of BA from other causes of neonatal cholestasis. Methods A twelve-point scoring system was proposed according to clinical, laboratory, ultrasonographic, and histopathological parameters. A total of 135 patients with neonatal cholestasis in two sets were recruited to design (n = 60) and validate (n = 75) a scoring system. Parameters with significant statistical difference between BA (n = 30) and non-BA (n = 30) patients in the design set were analyzed by logistic regression to predict the presence or absence of BA then a scoring system was designed and validated. Results The total score ranged from 0 to 37.18 and a cut-off value of >23.927 could discriminate BA from other causes of neonatal cholestasis with sensitivity and specificity of 100% each. By applying this score in the validation set, the accuracy was 98.83% in predicting BA. The diagnosis of BA was proposed correctly in 100% and the diagnosis of non-BA was proposed correctly in 97.67% of patients. By applying this model, unnecessary intraoperative cholangiography would be avoided in non-BA patients. Conclusions This scoring system accurately separates infants with BA and those with non-BA, rendering intraoperative cholangiography for confirming or excluding BA unnecessary in a substantial proportion of patients.