This paper reports the development of hybrid copolymer poly vinyl alcohol hydrogel (H-PVA) based on acrylic acid (AA), 2-acrylamido-2-methyl propane sulfonic acid (AMPSA) and ethylene glycol dimethacrylate (EGDMA). The H-PVA hydrogels were used for controlled release study of highly water-soluble antidepressant drug (venlafaxine). The formation of new structure was confirmed by Fourier transform infrared spectroscopy. The morphology of dry hydrogel slabs was examined by scanning electron microscopy. Thermal gravimetric analysis of hydrogels showed that there was an increase in thermal stability of H-PVA hydrogels. Swelling experiments performed in acidic and basic media provided important information on drug release properties of hydrogels. The release of venlafaxine was significantly retarded in pH 1.2, while rapid release was observed in pH 7.4. The release rate of venlafaxine increased with increasing ratio of AA and AMPSA. However, extent of drug release was significantly reduced on increasing ratio of EGDMA. Mechanism of release has been analyzed using various mathematical models. H-PVA hydrogel slabs were able to sustain the release of venlafaxine more than 20 h. The results of the study suggest that optimized H-PVA hydrogels could serve as suitable controlled release matrices.