Cross-linked poly (vinyl alcohol) (PVA) is a prolonged-release micromatrix, a hydrophilic polymer and a potentially interesting hydrogel, which is useful for drug delivery applications. As a part of drug development procedure the aim of this study was to investigate the effect of structural changes on drug release (theophylline) from this polymeric network. The studied parameters included: cross-linking agent (glutaraldehyde) concentration, PVA content of the films, theophylline percentage and their overall effect on swelling of the hydrogels, drug loading efficiency, diffusion and release characteristics of theophylline from PVA films. Changes in glutaraldehyde percentage (or cross-linking density) affected the swelling of the films. However, increasing PVA percentage caused more swelling, Drug loading efficiency was higher in gels with higher glutaraldehyde, PVA and theophylline percentages. Increasing contents of PVA and theophylline promoted the diffusion coefficient and drug release rate but glutaraldehyde had a reverse effect. The pH did not affect the swelling and diffusion coefficient. Water transport and drug release mechanism predominantly followed a Fickian model. It may be concluded that by changing the PVA structural parameters, a rate-controlled drug release is obtained.