ObjectiveTo evaluate the efficacy and safety of heated humidified high-flow nasal cannula (HHHFNC) vs. nasal continuous positive airway pressure (NCPAP) in the treatment of neonatal respiratory distress syndrome (NRDS). MethodsThe PubMed, EMbase, The Cochrane Library (Issue 3, 2017), CBM, VIP, WanFang Data and CNKI were searched up to March 27th, 2017 to collect randomized controlled trials (RCTs) of HHHFNC vs. NCPAP for NRDS. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed by RevMan 5.3 software.ResultsA total of 11 RCTs involving 1 104 patients were included. The results of meta-analysis showed that: 1) The HHHFNC group reduced the rate of reintubation (OR=0.56, 95%CI 0.32 to 0.98, P=0.04), shortened the time of assisted ventilation (MD=–11.12, 95%CI –13.31 to –8.93, P<0.000 01), hospitalization time (MD=–2.99, 95%CI –3.54 to –2.44, P<0.000 01) and neonatal aspiration of milk (MD=–17.82, 95%CI –21.19 to –14.45, P<0.000 01), shortened partial pressure of carbon dioxide at 48 hours (MD=–4.86, 95%CI –5.94 to –3.78, P<0.000 01), reduced the rate of frequent hemorrhoid (OR=0.32, 95%CI 0.12 to 0.90, P=0.03), the rate of abdominal distension (OR=0.17, 95%CI 0.09 to 0.30, P<0.000 01), the rate of injury of nose (OR=0.08, 95%CI 0.03 to 0.20, P<0.000 01), and the rate of head shape change (OR=0.03, 95%CI 0.00 to 0.23, P=0.000 7). 2) There were no significant differences between two groups in mortality rate, nosocomial infection rate, oxygen exposure time, arterial oxygen pressure and oxygen saturation at 48 hours, intraventricular hemorrhage, patent ductus arteriosus, retinopathy of prematurity, bronchopulmonary dysplasia and neonatal necrotizing enterocolitis, respectively. ConclusionCurrent evidence indicates that HHHFNC can reduce the rate of reintubation, shorten the time of assisted ventilation, length of hospital day and neonatal aspiration of milk, reduce the rate of frequent hemorrhoid, abdominal distension, injury of nose, head shape change. Due to the limitation of quantity and quality of included studies, the long-term follow-up results of HHHFNC for NRDS are needed to analyze with large-scale and multicenter RCTs.