A series of substituted 2- chloro-N-(4-phenylthiazol-2-yl) acetamide derivatives (4a-g) have been synthesized in good to excellent yield from the reaction between 2-aminothiazole with chloroacetyl chloride by alternative routeand evaluated as potential antibacterial agents. Among them, compounds 4a, 4b, 4e showed the potent antibacterial activity against Gram positive bacteria Bacillus subtilis andGram negative bacteria Salmonella typhimurium. The synthesized substituted 2- chloro-N-(4-phenylthiazol-2-yl) acetamide derivatives (4a-g) were tested atthree concentrations (25 μg/ml, 50 μg/ml and 100 μg/ml) and results were expressed in terms of zone of inhibition in millimeters by agar well diffusion method. The Ampicillin 1mg/ml was used as reference standard drug. The structures of synthesized compounds were assigned on the basis of IR, 1H NMR, 13C NMR and mass spectroscopy.