The main objective of this study was to assess the effects and mode of action of crude preparation of garlic (Allium sativum) on clinical isolates of Pseudonomas aeruginosa and Staphylococcus aureus from Nigeria. An experimental study was conducted in Department of Medical Microbiology & Parasitology, University College Hospital, Ibadan, Nigeria by agar dilution technique. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of garlic to control strains of Staphylococcus aureus ATTC 25923 and to clinical isolates of S. aureus and P. aeruginosa were determined using agar dilution method. All the tested organisms were inhibited by 134mg/ml for P. aeruginosa and 201mg/ml for S. aureus of the crude preparation of garlic except control organism and clinical isolates of S. aureus, which were inhibited by 201mg/ml of crude garlic extract. The study showed that in the absence of the extract, the cells grew to high densities within 1 h 30 min at 37 OC. Cells treated with garlic extract reduced in number and died. Percentage of viable at 201 mg/ml was 0% for both bacteria. Sucrose and MgSO4 stabilized and protected the cells. At 67, 134 and 201 mg/ml of the extract in the presence of this Sucrose and MgSO4, 47, 4 and 0% of P. aeruginosa cells were viable. Microscopic examination of carbol fuschin and Giemsa stained cells showed that the garlic treated cells were bigger in size than those of untreated ones; and intact and definite nuclei were lacking. The differences could be attributed to the genetic differences among the organisms and differences in the modes of action of the garlic extracts. No isolates were resistant to garlic, making it a promising antimicrobial agent. From the findings, it appears that the cell wall of these test bacteria was the target of attack and the extract was bacteriolytic in action. It also appears that the garlic extract interfere with DNA and RNA syntheses, this could constitute an effective partner in the synergic effect of garlic currently being investigated worldwide. Further studies are also recommended to investigate the detail steps involved in the mechanism of action of garlic extracts. Crude preparation of garlic could be used as an effective antibacterial agent for the tested bacteria. We hoped that this study would lead to the establishment of some new and more potent antimicrobial drugs from natural origin and native plants. Nevertheless, clinical trial on the effect of garlic is essential before advocating largescale therapy.