The present communication deals with the synthesis of some N´-alkylidene/arylidene-2-(4-substituted-5-phenyl-1,3,4-oxadiazol-2-ylthio) aceto/arylhydrazides, their characterization and antimicrobial activity against medically important microbes. The final compounds were synthesized by reaction of 2-(4-substituted-5-phenyl-1,3,4-oxadiazol-2-ylthio) acetohydrazide with various aliphatic and aromatic aldehydes in presence of glacial acetic acid in ethanol. The structures of the synthesized compounds were established by IR, NMR and Mass spectral studies. The antimicrobial activity was studied against Staphylococcus aureus (MTCC 87), Bacillus subtilis (MTCC 121), Pseudomonas aeruginosa (MTCC 424), Escherichia coli (MTCC 40), Candida albicans (MTCC 183), Fusarium solani (MTCC 2935) using agar well diffusion method. Some of the tested compounds exhibited activity against all the microorganisms.  In particular, compounds 12, 19 and 22 were found to be active against all the tested bacterial strains and fungal strain Candida albicans. It was concluded that number and position of electron withdrawing substituents affects the activity.