The syntheses of well-defined 7-arm and 21-arm poly(N-isopropylacrylamide) (PNIPAM) star polymers possessing beta-cyclodextrin (beta-CD) cores were achieved via the combination of atom transfer radical polymerization (ATRP) and click reactions. Heptakis(6-deoxy-6-azido)-beta cyclodextrin and heptakis[2,3,6-tri-O-(2-azidopropionyl)]-beta-cyclodextrin, beta-CD-(N-3)(7) and beta-CD-(N-3)(21), precursors were prepared and thoroughly characterized by nuclear magnetic resonance and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. A series of alkynyl terminally functionalized PNIPAM (alkyne-PNIPAM) linear precursors with varying degrees of polymerization (DP) were synthesized via atom transfer radical polymerization (ATRP) of N-isopropylacrylamide using propargyl 2-chloropropionate as the initiator. The subsequent click reactions of alkyne-PNIPAM with beta-CD-(N-3)(7) and beta-CD-(N-3)(21) led to the facile preparation of well-defined 7-arm and 21-arm star polymers, namely beta-CD-(PNIPAM)(7) and beta-CD-(PNIPAM)(21). The thermal phase transition behavior of 7-arm and 21-arm star polymers with varying molecular weights were examined by temperature-dependent turbidity and micro-differential scanning calorimetry, and the results were compared to those of linear PNIPAM precursors. The anchoring of PNIPAM chain terminal to beta-CD cores and high local chain density for star polymers contributed to their considerably lower critical phase separation temperatures (T-c) and enthalpy changes during phase transition as compared with that of linear precursors. (C) 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 404-419, 2009