The antipyretic effect of nimesulide has not been adequately compared with paracetamol and ibuprofenparacetamol combination in children. Hence, a randomized, double blind, and parallel groups’ design and multicenter study was conducted on children with respiratory tract infections. Eighty-nine patients with temperatures above 38.5°C were randomly administered nimesulide (1.5 mgJkgJdose), paracetamol (10.0 mgJkgJdose), or ibuprofen-patients combination (10.0 mgJkgJdose), thrice daily for five days. The axillary temperature was recorded at the baseline and at different time intervals post administration of drugs. The hematological and biochemical investigations were performed at the basal level and at the end of the treatment period. The adverse drug reactions were monitored during the trial. All the drugs produced a significant fall in temperature as compared to their respective basal values (p<0.001). However, on looking at the change in temperatures at different time intervals from the respective basal levels, no significant difference was found among all the drugs. Surprisingly, nimesulide had a tendency to raise serum glutamate pyruvate transaminase and serum glutamate oxaloacetate transaminase levels as compared to its baseline values. There was no marked adverse effect of the drugs on other hematological and biochemical parameters investigated. No other serious adverse reaction occurred in the study. Ibuprofen-paracetamol combination, nimesulide, and paracetamol had almost similar antipyretic effects in children.