Background: Seizures are the foremost common manifestation of neurological insult during the time of life. There are not any evidence-based guidelines for the pharmacologic treatment of neonatal seizures and management is highly variable. Hence this study was conducted with the target to match the efficacy and adverse effects of levetiracetam and phenobarbitone used for treatment of neonatal seizures.Methods: Open labelled, randomized controlled trial done in Special new-born care unit (SNCU) on 80 neonates (0-28 days) with clinical seizures.If seizures persisted even after correction of hypoglycemia and hypocalcemia, participants were randomized to receive either Levetiracetam (20 mg/kg) or Phenobarbitone (20 mg/kg) intravenously. The dose of same drug was repeated if seizures persisted (20 mg/kg of Levetiracetam or 10 mg/kg of Phenobarbitone) and change over to other drug occurred if the seizures persisted even after second dose of same drug. Results: Seizures stopped in 35(87.5%) and 23(57.5%) neonates in Levetiracetam and Phenobarbitone group, respectively(P value= 0.0047). 9 neonates had adverse reactions in the phenobarbitone group (hypotension in 4, bradycardia in 2 and requirement of mechanical ventilation in 3 neonates) while none had any adverse reaction in Levetiracatam group. Conclusions: Levetiracetam achieves better control than Phenobarbitone for neonatal seizures when used as first-line antiepileptic drug and is not associated with adverse drug reactions.