CONTEXT Surfactant nebulization (SN) may offer a safe alternative for surfactant administration in respiratory distress syndrome of preterm infants. OBJECTIVE To evaluate the efficacy of SN for the prevention of early intubation. DATA SOURCES Medline, Embase, The Cochrane Library, clinicaltrials.gov, published abstracts, and references of relevant articles were searched through March 23, 2021. STUDY SELECTION Randomized clinical trials of preterm infants <37 weeks’ gestation comparing SN with noninvasive respiratory support or intratracheal surfactant application. DATA EXTRACTION Two reviewers extracted data and assessed risk of bias from included studies separately and blinded. Data were pooled by using a fixed-effects model. Subgroups (gestational age, type of nebulizer, surfactant type, and dosage) were evaluated. Primary outcome was intubation rate at 72 hours after birth. RESULTS Nine studies recruiting 1095 infants met inclusion criteria. SN compared with standard care significantly reduced intubation rate at 72 hours after birth (226 of 565 infants [40.0%] vs 231 of 434 infants [53.2%]; risk ratio [RR]: 0.73, 95% confidence interval [CI]: 0.63–0.84; number needed to treat: 8; 95% CI: 5–14]). Prespecified subgroup analysis identified important heterogeneity: SN was most effective in infants ≥28 weeks' gestation (RR: 0.70, 95% CI: 0.60–0.82), with a pneumatically driven nebulizer (RR: 0.52, 95% CI: 0.40–0.68) and in infants receiving ≥200 mg/kg and animal-derived surfactant (RR: 0.63, 95% CI: 0.52–0.75). No differences in neonatal morbidities or mortality were identified. LIMITATIONS Quality of evidence was low owing to risk of bias and imprecision. CONCLUSIONS SN reduced the intubation rate in preterm infants with a higher efficacy for specific subgroups. There was no difference in relevant neonatal morbidities or mortality.