Objective To compare the effect of self-inflating bag (SIB) vs. T-piece resuscitator (TPR) on PaCO 2 levels, when used for brief manual ventilation during administration of first dose of surfactant. Methods Preterm neonates were randomized to receive positive pressure ventilation with either self-inflating bag or T-piece resuscitator during administration of first dose of surfactant. Arterial blood gases were obtained at baseline and 1 h after the intervention. Primary outcome was the mean change in PaCO 2 levels 1 h after the intervention. Results Eighty neonates were enrolled (40 in each group). The drop in PaCO 2 at 1 h was significantly greater in the self inflating bag group as compared to the T-piece resuscitator group [8.96 ± 9.06 mmHg vs. 1.37 ± 9.06 mmHg, Mean difference = 7.58 mmHg, (95% CI: 3.78 to 11.4); P < 0.01]. The PaCO 2 change was also statistically significant in the subgroup of infants that required only non-invasive ventilation. The need for second dose of surfactant was higher in the self-inflating bag group [77% vs. 55%, RR-1.41 (95% CI: 1.02 to 1.94); P = 0.03]. Conclusions T-piece resuscitator results in smaller reduction in PaCO 2 levels compared to the self inflating bag, when used for brief manual ventilation during surfactant administration.