We prospectively observed 62 pre-term very low birth weight neonates initiated on nasal continuous positive airway pressure (CPAP) for respiratory distress in the first 24 h of life to devise a clinical score for predicting its failure. CPAP was administered using short binasal prongs with conventional ventilators. On multivariate analysis, we found three variables-gestation <28 weeks [adjusted odds ratio (OR) 6.5; 95% confidence interval (CI) 1.5-28.3], pre-term premature rupture of membranes [adjusted OR 5.3; CI 1.2-24.5], and product of CPAP pressure and fraction of inspired oxygen ≥1.28 at initiation to maintain saturation between 88% and 93% [adjusted OR 3.9; CI 1.0-15.5] to be independently predictive of failure. A prediction model was devised using weighted scores of these three variables and lack of exposure to antenatal steroids. The clinical scoring system thus developed had 75% sensitivity and 70% specificity for prediction of CPAP failure (area under curve: 0.83; 95% CI 0.71-0.94).