A series of acrylamide (AAm)-based hydrogels containing acrylic acid, 2-acrylamido-2-methyl-1-propanesulfonic acid (AMPS), and vinyl imidazole (VI) comonomers were prepared by free radical polymerization. Silver nanoparticles were loaded to hydrogel systems through in situ reduction of silver nitrate in the presence of sodium borohydride as a reducing agent. The synthesized hydrogels and their composites were characterized using FTIR, scanning electron microscopy, EDX, and EDX-mapping. The antimicrobial activity of hydrogel-silver composite was determined using well agar and broth dilution tests. In the first stage, four different hydrogel-silver composites were evaluated against six different microorganisms using the well agar technique. The most effective hydrogel-silver composite among all tested was poly(AAm-co-VI-co-AMPS)-Ag, while the most sensitive and resistant microorganisms among all tested were Staphylococcus cerevisiae and S. aureus, respectively. Poly(AAm-co-VI-co-AMPS)-Ag composite was used in modeling the inhibition kinetic of Escherichia coli. The present study displays that hydrogel-silver composite has considerable antimicrobial activity, which deserves further investigation for use in clinic application and industrial processing.