BackgroundPulmonary surfactants(PS) combined with the intratracheal instillation of budesonide to prevent bronchopulmonary dysplasia (BPD) have been report previously. However, the safety of the use of PS combined with budesonide is still unknown and remains to be clarified. MethodsPubMed, the CochraneLibrary, EMBASE, the China Knowledge Network and the Wanfang database were searched for relevant studies. Searches were performed from December 2018, and data from randomized controlled trials (RCTs) were collected. Primary outcome measures were BPD incidence, BPD-related mortality. Secondary outcomes were BPD-related complications. The Cochrane risk assessment tool was used for the evaluation of bias. RevMan5. 3software was employed for metaanalysis. An Egger's test was used for publication bias assessments. ResultsA total of 720 subjects were enrolled from 6 RCTs, including 352 in the experimental group and 368 in the observation group. A meta-analysis showed that the incidence of BPD RR=0. 42, 95% CI (0. 37, 0. 89), P < 0.001 and BPD-related mortality RR = 0.54, 95% CI (0.38, 0.89), P<0.05 significantly differed between the groups. Differences were also observed for intraventricular hemorrhage, infection/sepsis, retinopathy of prematurity (ROP), and patent ductus arteriosus. There were no significant differences in the incidence of PDA, neonatal necrotizing enterocolitis (NEC), hyperglycemia, or hypertension (P > 0.05). ConclusionThe intratracheal instillation of pulmonary surfactants with budesonide can reduce the incidence of BPD and BPD-related mortality, with no increased risk of short-term complications. However, considering both sample size and study bias, the safety and efficacy of this treatment plan requires clarification in large-samples, and multi-center clinical RCTs. In addition, the impact of long-term complications such as neurodevelopmental disorders requires further assessment.