Several 3-substituted 1,2-benzisoxazole derivatives were synthesized from treatment of 4-amino- 2-hydroxy acetophenone by different aldehyde substitution with the hope that different substituent formed at the third position show significant antimicrobial activity. 4-amino-2- hydroxy acetophenone 1 on treatment with different aldehydes 2a-e in sodium hydroxide afford 3a-e. Compounds 3a-e on oximation yields 4a-e. Compounds 4a-e on treatment with silica gel and sodium carbonate affords 5a-e. The resultant 3-substituted 1,2-benzisoxazole derivatives have been characterized by spectral data. The compounds 5a-e have been screened for their antimicrobial activity. Compounds 5a, 5b and 5e exhibit good antimicrobial activity.