The diffusion of methyl ethyl ketone (MEK)/1-butanol (BOH) mixtures in polyisobutylene (PIB) was studied using time-resolved FTIR-ATR spectroscopy at varying mixture compositions. Diffusion coefficients and hydrogen-bonding interactions were quantitatively measured using this technique. In the MEK/BOH/PIB system, three species were identified from the infrared spectra, free MEK, an MEK-BOH complex, and a self-associated BOH cluster. The diffusion coefficient for the MEK-BOH complex was less than that for free MEK, but larger than the values determined for the BOH cluster. These results were compared to a numerical solution of a multicomponent transport model that explicitly accounts for solute–solute interactions to determine individual diffusion coefficients for all the species identified. In addition, the MEK/BOH/PIB results were compared to those for an MEK/acetonitrile (ACN) mixture, a nonhydrogen-bonding system, in PIB, to elucidate the differences between interacting and noninteracting systems.