The antimicrobial activities and preliminary phytochemical screening of methanolic extract of Vitellaria paradoxa was performed against clinical isolates obtained from UITH which included Staphylococcus aureus, Escherichia coli, Aspergillus niger and Candida albicans. Leaf extracts of Vitellaria paradoxa were prepared using methanol as solvent. The extracts were tested using agar diffusion and broth dilution method . Escherichia coli was resistant to all the extracts of Vitellaria paradoxa . Antimicrobial activity was recorded by the methanolic extract of Vitellaria paradoxa with zone of inhibition of 19mm on Candida albicans. The minimum inhibitory concentration of the extract ranged from 40mglml to 160mglml for Vitellaria paradoxa leaf extract. Methanolic leaf extract of Vitellaria paradoxa are found to be bactericidal and fungicidal on Staphylococcus aureus and Aspergillus niger, Candida albicans respectively. Vitellaria paradoxa leaf extract contained saponin, tannins, flavonoid, phenolics, steroids, alkaloids, phlobatannins and glycoside. The result from this study ,therefore suggest the possibility of using Vitellaria paradoxa extracts as antimicrobial agents, which can be a great asset to drug development for purpose of health care delivery in Nigeria