Background: Depressed neonates born through meconium stained amniotic fluid (MSAF) are at high risk for developing meconium aspiration syndrome (MAS). Benefits and risk of endotracheal suctioning in non-vigorous infants at birth, though widely practiced till recent have not been established. Objectives: To evaluate effect of endotracheal suctioning at birth on incidence of MAS, its severity and outcome among non-vigorous MSAF born infants. Methods: This randomized open level trial was conducted over one year period at a tertiary care teaching hospital. 155 non-vigorous infants (vigour assessed within 5-10 s of birth) were randomized to receive either endotracheal (ET) suctioning just after birth (n = 76) or no-endotracheal suction (n = 79). Subsequent resuscitation was performed as per neonatal resuscitation guideline. All infants were admitted for subsequent care and monitoring. Antenatal, intrapartum, and neonatal details; respiratory support; complications, hospital stay and outcome were recorded. Results: Incidence of respiratory distress due to MAS (with consistent chest radiology) was 41.3% and 57.1% [OR = 0.53(0.28to 1.01); p = 0.052], while non-MAS respiratory distress was 33.3% and 27.3% [OR = 1.69(0.81 to 3.54); p = 0.17] in ET suction and no-ET suction group, respectively. Severity of MAS in ET suction vs. no-ET suction group were mild:16.1%(5/31)vs15.9%(7/44); moderate:61.3%(19/31)vs65.9%(29/ 44) and severe:22.6%(7/31)vs18.2% (8/44). Respiratory support requirement including mechanical ventilation; its duration, and mortality were similar in both groups, however, hospital stay was shorter in ET suction group (9.91 ± 3.22vs. 11.17 ± 3.73 days; mean diff:−1.26(−3.36 to −0.17); p = 0.024). Conclusions: Endotracheal suctioning at birth in non-vigorous infants born through MSAF tends to decrease the incidence of MAS and duration of hospital stay, however, overall incidence of respiratory distress and mortality remain unchanged.