Three nonsteroidal antiinflammatory drugs, 2-(4-isobutylphenyl)-propionic acid (ibuprofen), 2-(3-benzoylphenyl)-propionic acid (ketoprofen), and 2-(6methoxy-2-naphthyl)-propionic acid (naproxen), were covalently linked with 2-hydroxyethyl methacrylate (HEMA). The drug-linked HEMA (M 1 ) (ibuprofen-linked HEMA abbreviated as HI; ketoprofen-linked HEMA as HK, and naproxen-linked HEMA as HN), were respectively copolymerized with methacrylic acid (M 2 ), MA, to obtain macromolecular prodrugs. The compositions of the copolymers were determined by means of a 1 H-NMR spectroscopy and monomer reactivity ratios were estimated using the Kelen-Tu ¨do ¨s linear differential equation. The reactivity ratios are: r 1 Å 0.101 { 0.012, r 2 Å 1.071 { 0.065 for HI-MA; r 1 Å 0.344 { 0.066, r 2 Å 0.966 { 0.032 for HN-MA, and r 1 Å 0.650 { 0.182, r 2 Å 1.032 { 0.106 for HK-MA, respectively. The monomer reactivity toward to MA radical estimated from 1/ r 2 values is almost same for all three monomers (1/r 2 Ç 1). The glass transition temperatures of three drug-linked homopolymers go hand in hand with the steric hindrance of three drugs, i.e., ketoprofen ú naproxen ӷ ibuprofen calculated the minimum energy by computer molecular modeling.