Poly(vinyl alcohol)s (PVA) with high and low molecular weights were chemically modified by introducing acetaldehyde onto the polymer backbone to induce thermal-responsive properties. The influence of both molecular weight ( ) and acetalization degree on the lower critical solution temperature (LCST) of thermo-sensitive polymer was investigated. Moreover, a temperature responsive hydrogel was prepared by controlled cross-linking of acetalized poly(vinyl alcohol) (APVA) and glutaraldehyde. As a model drug, ciprofloxacin was introduced into the prepared thermal sensitive hydrogel to reveal the drug loading and release behaviors. The structure, thermo-sensitivity, swelling/deswelling kinetics, morphology, and drug loading/release behaviors were also investigated. The results indicated that the APVA polymer solution exhibited temperature responsivity, and APVA with high acetalization degree showed low LCST, whereas those with high PVAs showed high LCST. Meanwhile, morphology study was identical with the swelling/de-swelling behavior. The loading and release of ciprofloxacin were controllable. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 39720.