A new series of 5-(p-substituted benzamido/phenylacetamido)-2-(p-tert-butylphenyl)ben-zoxazole derivatives were synthesized and evaluated for their antibacterial, antifungal, and antimycobacterial activities against antibiotic-resistant and -sensitive Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, and Mycobacterium tuberculosis as well as against Candida albicans and Candida krusei. The compounds possessed broad-spectrum activity against all of the tested Gram-positive and Gram-negative bacteria and yeasts, their minimum inhibitory concentrations (MICs) ranging between 16-128 μg/ml. One compound exhibited signifi cant antibacterial activity (16 μg/ml) against an antibiotic-resistant Enterococcus faecalis isolate, having twice the potency of the compared standard drugs vancomycin and gentamycin sulfate. The compounds also showed moderate antitu-bercular activity with MIC values between 8-128 μg/ml against Mycobacterium tuberculosis and its clinical isolate. © 2013 Verlag der Zeitschrift für Naturforschung, Tübingen.