The aim of this study was to evaluate the efficacy and safety of a standardized protocol of delivery room CPAP therapy in late preterm infants with acute neonatal respiratory failure (ARF) caused by various conditions.Material and methods. A retrospective comparative study of the efficacy of the standardized CPAP protocol in the cohorts of late preterm infants (34–36 weeks) was conducted at the Yekaterinburg Perinatal Center. The comparison group (C, N=256) included infants who received CPAP therapy in the delivery room during 12 months in 2020 before the introduction of the standardized protocol. The study group (S, N=169) included infants treated with standardized CPAP in April-December, 2022. The following subgroups were identified in groups C and S based on the cause of ARF: transient tachypnea of the newborn (TTN; C: N=100; S: N=89), respiratory distress syndrome (RDS; C: N=84; S: N=39), and congenital infection (CI; C: N=54; S: N=37). Other causes of ARF in groups C and S were found in 18 and 4 infants, respectively.Results. Switching to the standardized CPAP protocol reduced the duration of mechanical ventilation by an average of 24 h (P=0.013), the incidence of documented cerebral ischemia (CI) from 64.1% to 53.2% in all subgroups (P=0.022), the length of stay in the neonatal ward from 12 to 11 days (P=0.001), and the length of stay in the hospital from 16 to 14 days (P=0.001) as well as the incidence of CI in the STTN subgroup vs CTTN (38.2% vs. 61.0%, P=0.002). No significant differences were found in the RDS and CI subgroups. The frequency and duration of binasal CPAP and lung ventilation in the neonatal ICU did not differ between subgroups. Pneumothorax within the first 24 h occurred in one patient in group C and in two patients in group S (P=0.339), all of whom were diagnosed with congenital infection. No damage to the nasal passages was observed in any group. Conclusion. The use of a standardized protocol of CPAP therapy for neonates born after 35 weeks of gestation with respiratory failure of any etiology can significantly reduce the severity and duration of illness and should be considered as a basic respiratory strategy in the delivery room when indicated.