Aim: This study compares the efficacy of fusidic acid and mupirocin in treatment of impetigo. Materials and Methods: This was an open label; prospective clinical study was carried out among 60 impetigo patients. The primary end points were evaluated at the baseline, and after one week of treatment. In both groups the test drug was applied locally thrice daily. Statistical analysis was done using paired and unpaired t test. Results: In group I and II; mean number of lesions declined from 4.64 to 0.44 and 4.35 to 0.16 and mean lesion size declined from 3.28 to 0.18 and 3.44 to 0.11 (p≤0.05) respectively. Conclusion: Mupirocin is marginally more effective than fusidic acid but this difference was not statistically significant.