This study describes a versatile strategy combining reversible addition fragmentation transfer (RAFT) polymerization and click chemistry to synthesize well-defined, reactive copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) for drug delivery applications. A novel azide containing monomer N-(3-azidopropyl)methacrylamide (AzMA) was synthesized and copolymerized with HPMA using RAFT polymerization to provide p(HPMA-co-AzMA) copolymers with high control of molecular weight (approximate to 10-54 kDa) and polydispersity (1.06). The utility of the side-chain azide functionality by Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) was demonstrated by efficient conjugation (up to 92%) of phosphocholine, a near infrared dye, and poly(ethylene glycol) (PEG) with different substitution degrees, either alone or in combination. This study introduces a novel and versatile method to synthesize well-defined click-reactive HPMA copolymers for preparing a panel of bioconjugates with different functionalities needed to systemically evaluate and tune the biological performance of polymer-based drug delivery. (c) 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 5091-5099