The search for compounds with antimicrobial activity has gained increasing importance in recent times, due to growing worldwide concern about the alarming increase in rate of infection by antibiotic-resistant microorganisms. Antibacterial activity of the ethanolic leaf extracts of Andographis paniculata against Staphylococcus aureus and Escherichia coli was studied. The fresh leaves of Andographis paniculata were collected randomly from a local farm in Alulu Enugu East L.G.A Enugu State Nigeria. The leaf samples were morphologically identified, washed, air dried at room temperature and milled into powder. Thirty-nine grams of the powder total weight of the extract, was macerated using ethanol as solvent. Phytochemical analysis of the leaves extract was carried out and the results showed that Saponins (++), Tannins (++), Flavonoids (+++), Phenols (+++), Steroids (++) were present while Terpenoids (-), Alkaloids (-) and Glycosides (-) were absent. The extract was concentrated by evaporation at various concentrations (100mg/ml, 300mg/ml, and 500mg/ml) prepared using 5% DMSO. Antibacterial activity was determined using agar well diffusion method, and results showed that there was no antibacterial activity of ethanolic leaf extracts of A. paniculata against E. coli while there was inhibition zones of 20 mm, 17 mm and15 mm against Staphylococcus aureus respectively. The Minimum inhibitory concentration was determined and the results showed that at 12.5mg/ml concentration, the extract was able to inhibit the growth of Staphylococcus aureus. The Minimum inhibitory concentration was determined and the results showed that at 12.5mg/ml concentration, the extract was able to inhibit the growth of Staphylococcus aureus. This study therefore showed that ethanolic extracts of Andographis paniculata has activity against the Staphylococcus aureus since they exhibited comparable activity with the positive control ciprofloxacin.