A series of 2-(p-substituted phenyl)-5-(2-{4-[(p-chloro-fluorophenyl)/phenyl] piperazin-1-yl}acetamido)-benzoxazoles were synthesized and tested for their antimicrobial activities. The structures of the new derivatives were elucidated by spectral techniques. The minimum inhibitory concentrations (MIC) of the new benzoxazoles, along with those of previously synthesized analogues, were determined against standard bacterial and fungal strains and drug-resistant isolates, and compared with those of several reference drugs. The new benzoxazole derivatives were found to possess a broad spectrum of antimicrobial activity with MIC values of 32-1024 μg/ml. Although the standard drugs were more active against the tested pathogens, the activities of the new benzoxazoles and the reference drugs were largely similar against the drug-resistant isolates.