ABSTRACTNovel amphiphilic copolymeric gels were developed to immobilize lipase. NIPA‐co‐PEGMEA gels were prepared by copolymerizing N‐isopropylacrylamide (NIPA) as a thermosensitive and amphiphilic component and poly(ethylene glycol) methyl ether acrylate (PEGMEA) as a hydrophilic component in aqueous media. The gels can absorb organic solvents at temperatures higher than the lower critical solution temperature owing to the thermosensitive and amphiphilic properties of poly(NIPA). The lipase immobilized within the NIPA‐co‐PEGMEA gel, which had a NIPA : PEGMEA composition of 950 : 50 mol/m3, successfully catalyzed the esterification of oleic acid and ethanol without loss of activity during repeated use within 20–40°C. The activity of the immobilized lipase was considerably higher than that of free lipase. The NIPA‐co‐PEGMEA gels provide a structure that allows the immobilized lipase to work actively in an aqueous environment and with the dispersed state of the lipase in the gels. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41905.