In this paper we investigated the release kinetics of a model drug-like compound (Coomassie brilliant blue) from polyvinylalcohol (PVOH) films into ahydro-alcoholic solution as a function of the physicochemical properties of the polymer matrix. After 33 days of monitoring, the total amount released ranged from 10% for the high hydrolysis degree/low molecular weight PVOH films to 60% for the low hydrolysis degree/low molecular weight films. Mathematical modeling allowed for an estimation of the two diffusion coefficients ( D 1 and D 2 ) that characterized the release profile of the dye from the films. The degree of hydrolysis dramatically affected both the morphology and the physical structure of the polymer network. A high hydroxyl group content was also associated with the shifting of second order and first order transitions toward higher temperatures, with a concurrent increase in crystallinity. Moreover, the higher the degree of hydrolysis, the higher the affinity of the polymer to the negatively charged molecule dye. Selection of the polymer matrix based on physicochemical criteria may help in achieving different release patterns, thereby representing the first step for the production of polymer systems with modulated release properties.