Background and aim: Neonatal respiratory distress syndrome is a leading cause of morbidity in preterm newborn babies (<37 weeks gestation age). The current diagnostic reference standard includes clinical testing and chest radiography with associated exposure to ionising radiation. The aim of this review was to compare the diagnostic accuracy of lung ultrasound against the reference standard in symptomatic neonates of 42 weeks gestation age. Methods: A systematic search of literature published between 1990 and 2016 identified 803 potentially relevant studies. Six studies met the review inclusion criteria and were retrieved for analysis. Quality assessment was performed before data extraction and meta-analysis. Results: Four prospective cohort studies and two case control studies included 480 neonates. All studies were of moderate methodological quality although heterogeneity was evident across the studies. The pooled sensitivity and specificity of lung ultrasound were 97% (95% confidence interval [CI] 94-99%) and 91% (CI: 86-95%) respectively. False positive diagnoses were made in 16 cases due to pneumonia (n ¼ 8), transient tachypnoea (n ¼ 3), pneumothorax (n ¼ 1) and meconium aspiration syndrome (n ¼ 1); the diagnoses of the remaining three false positive results were not specified. False negatives diagnoses occurred in nine cases, only two were specified as air-leak syndromes. Conclusions: Lung ultrasound was highly sensitive for the detection of neonatal respiratory distress syndrome although there is potential to miss co-morbid air-leak syndromes. Further research into lung ultrasound diagnostic accuracy for neonatal air-leak syndrome and economic modelling for service integration is required before lung ultrasound can replace chest radiography as the imaging component of the reference standard.