Objective: To identify risk factors and neonatal outcomes associated with the early failure of “ bubble” nasal continuous positive airway pressure (CPAP) in very low birth weight (VLBW) infants with respiratory distress syndrome (RDS)-. Study design: Following resuscitation and stabilization at delivery, a cohort of 261 consecutively inborn infants (birth weight ≤ 1250 g) was divided into three groups based on the initial respiratory support modality and outcome at 72 hours of age: “ ventilator-started” group, “ CPAP-failure” group, and “ CPAP-success” group. Results: CPAP was successful in 76% of infants ≤ 1250 g birth weight and 50% of infants ≤ 750 g birth weight. In analyses adjusted for postmenstrual age (PMA) and small for gestational age (SGA), CPAP failure was associated with need for positive pressure ventilation (PPV) at delivery, alveolar-arterial oxygen tension gradient (A-a DO2) >180 mmHg on the first arterial blood gas (ABG), and severe RDS on the initial chest x-ray (adjusted odds ratio 95% CI = 2.37 1.02, 5.52 , 2.91 1.30, 6.55 and 6.42 2.75, 15.0 , respectively). The positive predictive value of these variables ranged from 43% to 55% . In analyses adjusted for PMA and severe RDS, rates of mortality and common premature morbidities were higher in the CPAP-failure group than in the CPAP-success group. Conclusion: Although several variables available near birth were strongly associated with early CPAP failure, they proved weak predictors of failure. A prospective controlled trial is needed to determine if extremely premature spontaneously breathing infants are better served by initial management with CPAP or mechanical ventilation. Objective: To identify risk factors and neonatal outcomes associated with the early failure of “bubble” nasal continuous positive airway pressure (CPAP) in very low birth weight (VLBW) infants with respiratory distress syndrome (RDS) -. Study design: Following resuscitation and stabilization at delivery, a cohort of 261 consecutively inborn infants (birth weight ≤ 1250 g) was divided into three groups based on the initial respiratory support modality and outcome at 72 hours of age: “ventilator-started” group, “CPAP-failure” Results: CPAP was successful in 76% of infants ≤ 1250 g birth weight and 50% of infants ≤ 750 g birth weight. In analyzes adjusted for postmenstrual age (PMA) and small for gestational age (SGA), CPAP failure was associated with need for positive pressure ventilation (PPV) at delivery, alveolar-arterial oxygen tension gradient (Aa DO2)> 180 mmHg on the first arterial blood gas (ABG), and severe RDS on the in The positive predictive value of these variables ranged from 43% to 55%. In analyzes adjusted for for (adjusted odds ratio 95% CI = 2.37 1.02, 5.52, 2.91 1.30, 6.55 and 6.42 2.75, 15.0, respectively) PMA and severe RDS, rates of mortality and common premature morbidities were higher in the CPAP-failure group than in the CPAP-success group. Conclusion: Although several variables available near birth are strongly associated with early CPAP failure, they proved weak predictors of failure A prospective controlled trial is needed to determine if extremely premature spontaneously breathing infants are better served by initial management with CPAP or mechanical ventilation.