We investigated the hydrogen bonding of a small molecule to polymer chains by forced Rayleigh scattering, equilibrium binding, and computer simulation. Diffusion of 4-(4 '-(dimethylamino)phenylazo)benzoic acid (p-MR) was reported previously to be far more retarded in a toluene solution of poly(methyl methacrylate) (PMMA) or poly(vinyl acetate) (PVAc) than in a polystyrene solution due to the hydrogen bonding of the carboxylic hydrogen in p-MR with the carbonyl groups in PMMA or PVAc. In this study, we found that PVAc solution exhibits a more effective retardation of the p-MR diffusion than the PMMA solution despite their similar molecular structures. The difference in the p-MR diffusivity in PVAc and PMMA solutions could be attributed to the difference in binding efficiency of the probe dye onto the two polymers. In addition, the computer simulation calculation of the surface area of the carbonyl group of the polymer chains accessible for a small molecule to hydrogen bond showed a difference between the two polymers, which was consistent with the results of the diffusion and equilibrium binding studies.