Abstract Background: The effects of minimally invasive surfactant administration (MISA) in preterm infants with neonatal respiratory distress syndrome (NRDS) are unclear. Methods: We searched randomized controlled trials (RCTs) and compared MISA techniques with intubation for surfactant delivery in preterm infants with NRDS in PubMed, Embase, Cochrane Library, and Web of Science. Results: Thirteen RCTs (1931 infants) were included in the meta-analysis. The use of MISA techniques decrease the incidence of bronchopulmonary dysplasia (BPD) at 36 weeks, pneumothorax, and hemodynamically significant patent ductus arteriosus (hsPDA) (Risk Ratio(RR) : 0.59, 95% confidence interval (CI) : 0.46 to 0.75, p < .0001; RR : 0.60, 95% CI : 0.39 to 0.93, p= .02 and RR : 0.88, 95% CI : 0.78 to 1.00, p= .04, respectively). In addition, infants in the MISA group required less mechanical ventilation within 72 h of life or during hospitalization (RR : 0.60, 95% CI : 0.48 to 0.75, p< .00001 and RR : 0.64, 95% CI : 0.49 to 0.82, p = .0005, respectively) compared with infants in the control group. However, the rate of surfactant reflux was higher in the MISA group than that in the control group (RR : 2.12, 95% CI : 1.37 to 3.29, p = .0008). There were no significant differences in mortality and other outcomes beteween the MISA group and the control group. Conclusions: The administration of surfactant with MISA techniques could lower the requirement for mechanical ventilation, and decrease the incidence of BPD at 36 weeks, pneumothorax, and hsPDA.