Abstract Background: There are preliminary reports of the benefit of additional pulse methylprednisolone (MP) to oral prednisolone in the treatment of West syndrome. Aim: To compare the efficacy and safety of intravenous pulse MP followed by low-dose prednisolone versus low-dose prednisolone alone for children with West syndrome. Materials and Methods: This randomized, open-labeled, controlled clinical trial was conducted among children aged two months to 30 months with a diagnosis of West syndrome. They were randomized to either of pulse MP (30 mg/kg for 3 days) followed by low-dose prednisolone (2 mg/kg) [n = 26] or low-dose prednisolone (2 mg/kg) alone [n = 24] for four weeks. Results: The efficacy of pulse MP was comparable with oral prednisolone in terms of spasms cessation (11 [45.8%] vs. 7 [26.9%]; RRR [95% confidence interval [CI]: 0.74 [0.47–1.14]; P = 0.24), more than 50% spasms reduction (16 [66.6%] vs. 11 [42.3%]; RRR [95% CI]: 0.57 [0.31–1.12]; P = 0.09), more than 90% reduction (11 [42.8%] vs. 7 [26.9%]; RRR [95% CI]: 0.74 [0.47–1.14]; P = 0.24), and primary electroclinical remission (5 [20.8%] vs. 2 [7.6%]; RRR [95% CI]: 0.85 [0.68–1.08]; P = 0.21). The adverse effect profile was comparable in the two groups. Conclusion: Pulse MP therapy followed by oral prednisolone in low-dose (2 mg/kg) was as effective as low-dose prednisolone (2 mg/kg) therapy alone in West syndrome. Although pulse MP did not result in any adverse outcome, routine use of the same before initiation of oral prednisolone needs further studies with a larger sample size; longer follow-,up and comparative trial with high dose steroids (4 mg/kg).