A controlled/ living free-radical polymerization technique was introduced to prepared a homogeneous poly(N-isopropylacrylamide)-g-poly(sulfobetaine methacrylate) hydrogel (RG) possessing a highly porous architecture via two steps. Compared to a poly(N-isopropylacrylamide)-co-poly(sulfobetaine methacrylate) hydrogel (CG) prepared by conventional radical polymerization, RG exhibited a much faster shrinking rate (it lost over 72% of the water in 15 min) in response to the temperature changes. The release behaviors of tetracycline hydrochloride (TCHC) of the hydrogels indicated the TCHC release from the RG could be prolonged to 48 h at 37°C; this was much longer than that for CG (5 h at 37°C). Bovine serum albumin (BSA) was chosen as the model protein to examine the low-fouling properties of the RG. The BSA adsorption data showed that improved antifouling properties could be achieved by the RG at both 25 and 37°C. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 39816.