Objectives: With the increase in reports of the failure of Paracetamol as antipyretic in pediatric patients and the increase in the use of Mefenamic acid, the study was undertaken to recommend best among the both antipyretics by comparing the efficacy and tolerability of both these drugs. Methods-It was a prospective, active treatment controlled study with follow up to 72 hours done over a period of 2 months after the Institutional Ethical committee approval. Total 124 pediatric patients with fever admitted to Pravara Rural Hospital, Loni having a body temperature >38.5 and fulfilling the inclusion and exclusion criteria were included. Patients included were categorized into two groups –group A and group B and administered Paracetamol and Mefenamic acid in the doses 15 mg/kg and 4 mg/kg body weight respectively. The parameters essential for comparing the efficacy and tolerability were observed and recorded. The collected data were subjected to ‘paired t test’ of significance and was analyzed statistically. Results-Both drugs significantly decreased body temperature in pediatric patients with fever. The antipyretic efficacy of Mefenamic acid was highly significant than Paracetamol (<0.05). No significant differences in adverse effects were noted in both the groups. Conclusion-Mefenamic acid was found to be more effective and equally tolerable than paracetamol as an antipyretic in pediatric patients with febrile illness and can be the best alternative to paracetamol.