A series of cationic poly(N-isopropyl acrylamide) (PNIPAM)-g-poly(carboxybetaine ester) (PCBMAE) hydrogels were prepared by reversible addition–fragmentation chain-transfer polymerization with PCBMAE precursors reacting with N-isopropyl acrylamide in the presence of N,N′-methylene bisacrylamide. These hydrogels exhibited excellent antimicrobial activities against Staphylococcus aureus and could switch to nontoxic zwitterionic hydrogels after hydrolysis. Nonionic tetracycline hydrochloride (TCHC) and anionic sodium salicylate (SA) were selected to evaluate the loading capacities and release kinetics of the cationic hydrogels. We found that the loading efficiencies of TCHC in the PNIPAM-g-PCBMAE hydrogels were approximately twice as high as those of SA. However, the cumulative release amount of TCHC was lower than that of SA from the corresponding cationic hydrogel at 37°C. In addition, the PNIPAM-g-PCBMAE hydrogels exhibited accelerated release rates of both TCHC and SA with increasing content of (2-carboxymethyl)−3-acryloxyethyldimethylammonium chloride methyl ester. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 39839.