A set of 2-(p-substituted-benzyl)-5-[[4-(p-chloro/fluoro-phenyl)piperazin- 1-yl]acetamido]-benzoxazoles was evaluated for in vitro antimycobacterial activity against Mycobacterium tuberculosis and its isolate in comparison with reference drugs. The activity was expressed as minimum inhibitory concentration (MIC) in μg/ml. Compounds showed similar activity against test strains and most of them were more potent against M. tuberculosis than its isolate. Compound 9 exhibited a MIC value of 8 μg/ml against both of the tested microorganisms and had the highest activity among all derivatives. This microbiological assay showed that these benzoxazole derivatives possess a broad spectrum of antimycobacterial activity having MIC values of 8-64 μg/ml against the tested strains.