A new strategy integrating antimicrobial and nonfouling/biocompatible properties is presented. A mild antimicrobial agent (salicylate) was incorporated into a carboxybetaine ester hydrogel, poly(N,N-dimethyl-N-(ethylcarbonylmethyl)-N-[2-(methacryloyloxy)-ethyl]ammonium salicylate) (pCBMA-1 C2 SA) hydrogel, as its anionic counterion. This new hydrogel provides a sustained release of antimicrobial agents to inhibit the growth of planktonic bacteria and create a nonfouling surface to prevent protein adsorption or bacterial accumulation upon the hydrolysis of carboxybetaine esters into zwitterionic groups. The pCBMA-1 C2 SA hydrogel inhibited the growth of both gram-negative Escherichia coli K12 and gram-positive Staphylococcus epidermidis by 99.9%. This hydrogel holds great potential in applications such as wound dressing and surface coatings for medical devices.