Early use of continuous positive airway pressure (CPAP) is equal to the prophylactic administration of a surfactant to prevent neonatal respiratory distress syndrome (nRDS) in high-risk infants. However, almost half of the smallest infants still require intubation and mechanical ventilation in the first 72 hours after birth. It is known that ineffective initial CPAP is associated with a poorer prognosis. Therefore, the search for reliable prognostic risk factors for ineffective CPAP in very preterm neonates whose respiratory support is started with CPAP is still relevant today. The results of a retrospective cohort study conducted at the Lviv Regional Clinical Hospital (Ukraine), which included 151 children with birth weight <1500 g and gestational age <32 weeks, showed that CPAP failure occurred at a median age of five hours in 31% of infants initially treated with CPAP and average (SD) FiO2, while the failure point was 0.48 (0.15). The prevalence of the main risk factors for severe nRDS did not differ significantly between two groups (CPAP success and CPAP failure). The risk of CPAP failure was significantly associated with surfactant treatment (OR – 7.46; 95% CI: 2.3–24.2), severe RDS (OR – 12.17; 95% CI: 3.8–39.3), requirement in resuscitation after birth (OR – 3.10; 95% CI: 1.2– 8.1), initial CPAP pressure (OR – 0.38; 95% CI: 0.15–0.99). Earlier administration of exogenous surfactant to children at high risk of developing severe RDS could prevent the need for mechanical ventilation.