A monomer, vanillin oxime (VO), has been synthesized from vanillin and hydroxylamine hydrochloride, and its terpolymer resin VO-formaldehyde-p-hydroxyacetophenone (VOFHA) has also been synthesized by condensation of VO, formaldehyde, and p-hydroxyacetophenone (HA) in 1:2:1 M proportion in the presence of hydrochloric acid. The structures of monomer and terpolymer have been investigated by FT-IR and 1 H NMR techniques. The number-average molecular weight and polydispersity index of the terpolymer were found to be 5337.6 g/mol and 1.33, respectively, by gel permeation chromatography. Apparent activation energies of the thermal decomposition of the terpolymer were determined using the Flynn-Wall-Ozawa method. Terpolymer (VOFHA) has shown highest zone of inhibition as compare to other terpolymer and standard drugs. This novel bio-responsive antimicrobial terpolymer shows promise for use in the control of medical devices associated infections.