Antimicrobial activity of aqueous, methanol and chloroform leaf extracts of Cissus multistriata were investigated against 8 bacterial and 2 fungal test organisms, using the tube dilution and agar ditch diffusion methods. Aqueous leaf extract had no activity against both the bacterial and fungal test organisms. Both the methanol and chloroform leaf extracts inhibited all the test organisms with chloroform leaf extract showing the highest zone of inhibition against Escherichia coli (diameter 25 mm) and least against Staphylococcus aureus (diameter 13 mm). The methanol leaf extract was least inhibitory against Salmonella typhi (diameter 8 mm) and most inhibitory against S. aureus (diameter 15 mm). The methanol leaf extract of C. multistriata show more antifungal activity compared with chloroform leaf extract, with Candida albicans being more susceptible than Aspergillus niger to both methanol and chloroform leaf extracts. The minimum inhibitory concentration (MIC) of methanol leaf extract show least activity against Yersinia enterocolitica and Pseudomonas aeruginosa (MIC = 100 mg/ml) and higher activity of MIC at 50 mg/ml against the other bacterial test organisms. The chloroform leaf extract MIC of 100 mg/ml had least activity against Proteus mirabilis and P. aeruginosa and MIC of 20 mg/ml most inhibitory against E. coli, Klebsiella pneumonia and S. typhi. The antimicrobial activity of the heated extracts persisted after exposure to various temperatures between 30 o C to 121 o C for 15 to 30 min. However, the extract activity decreased as the temperature increased. The killing rate of the MBC of chloroform extract on E. coli was 1 cfu/3 min while on S. typhi was 1 cfu/3.8 min.