Aims: To compare efficacy of phenobarbital (PB), phenytoin (PHT) and lorazepam (LZP) for neonatal seizures. Settings: Medical College Hospital. Design: Prospective block design randomized trial (registration-CTRI/2012/12/003255). Subjects and Methods: Of 121 neonates with convulsions, 106 were grouped to receive PB (20 mg/kg), PHT (20 mg/kg) or LZP (0.05 mg/kg) intravenously over 5 min. The primary end point was clinical control of seizures within 2.5 min of starting single dose anti-epileptic drug (AED). Treatment was considered to have failed if the seizures lasted longer than 5 min, or a total of 2.5 min of seizure activity within 5 min period after a single dose. Statistical Analysis: Chi-square, Fisher's exact test, t-test, ANOVA. Results: Seizures subsided in 78 (74%) neonates within 2.5 min with a single dose, recurred in 55 (52%) and other AED was required in 30 (28%) neonates. 11% (10/89) required AED beyond discharge. The complete control of neonatal seizures within 2.5 min was similar with PB and PHT, but significantly more seizure control (89%) in the LZP group (P < 0.05). Adverse events (19%) were: PB - drowsiness 11; PHT - thrombophlebitis 3, nystagmus 1; LZP - drowsiness 2, hypotonia 3. 22 neonates expired (phenobarbitone 12, PHT 3, LZP 7). Conclusion: The complete control of 1st neonatal seizures within 2.5 min was similar with PB and PHT, but LZP had less treatment failure and less response time to control seizures. For control of recurrence and persistent seizure, none of the three drugs was better than the other. PB had the worst outcome as far as the deaths were concerned, followed by LZP and PHT.