As a part of our ongoing project on the design and synthesis of new thiazole derivatives with antimicrobial activity, fourteen new ethyl 2-(2-((E)-((Z)-5-(4-benzyliden)- 4-oxothiazolidin-2-yliden)amino-4-yl)acetates, carrying halogens, methoxy and other groups were synthesized. Compounds were tested against eight Gram positive and negative bacteria as well as eight yeasts and mold by microdilution assay. All compounds showed good activity against all bacteria tested with MIC ranging between 2.3-39.8 µmol/ml x 10-2 and MBC of 9.2-79.6 µmol/ml x 10-2. As reference drugs Ampicillin (MIC 24.8-74.4 and MBC 37.2-124.0 µmol/ml x 10-2) and Streptomycin (MIC 4,3-17.2 and MBC 8.6-51.6 µmol/ml x 10-2) were used. The best activity was observed for 4-bromo derivative. All tested compounds showed excellent antifungal activity against all fungi tested with MIC in the range between 0.3-38.6 µmol/ml x 10-2 and MFC range of 0.6-77.2 µmol/ml x 10-2, better than that of reference drugs, Ketoconazole (MIC 38.0-475.0 and MFC 95.0-570 µmol/ml x 10-2) and Bifonazole (MIC 48.0-64.0 and MFC 64.0-80.0 µmol/ml x 10-2). The best activity was observed for 3-nitro derivative. It was found that among the 5-arylidene derivatives the inhibitory effect appears to be dependent on the substitution at the benzene ring. Fourteen new ethyl 2-(2-((E)-((Z)-5-(4-benzyliden)-4-oxothiazolidin-2-yliden)amino-4-yl)acetates were synthesized and evaluated for antibacterial and antifungal activity.