A series of four random copolyesters were synthesized by the polycondensation of a chalcone diol with two diacid chlorides namely terepththaloyl chloride and glutaryl chloride. The four chalcone diols used are (2E)-1,3-bis-(4- hydroxyphenyl)-prop-2-en-1-one, (2E)-1-(4-hydroxyphenyl)-3-(4-hydroxy-3-methoxyphenyl)-prop-2-en-1-one, (2E)- 1-(4-hydroxy-3-methoxy phenyl)-3-(4-hydroxy phenyl)-prop-2-en-1-one and (2E)-1,3-bis-(4-hydroxy-3-methoxy phenyl)-prop-2-en-1-one were synthesized by acid catalyzed Claisen-Schmidt reaction. The random copolyesters were synthesized by solution polycondensation technique and they were characterized by qualitative solubility tests and viscosity measurements. The microstructure of the repeating units available in the copolyester backbone was established by FT-IR, 1H-NMR and 13C-NMR spectroscopic techniques. The inhibitory activity of the random copolyesters against certain microbes is well documented. Hence these random copolyesters may emerge as antimicrobial agents.