The objective of the present work was to develop modified release tablets of Isoniazid by using HPMC as a release-controlling agent. The different-viscosity grades of HPMC were used to prepare the matrix tablets. The tablets were prepared by direct compression. The prepared tablets were subjected to physical characterization and in vitro drug release studies. The in vitro drug release was carried out by using USP apparatus I in 900 ml of acidic dissolution medium (pH 1.2) for 2 h, followed by 900 ml alkaline dissolution medium (pH 6.8) at 50 rpm. The polymer type did not affect the flow of powder blend and crushing strength of Isoniazid tablets. The drug release rate was strongly influenced by the type of polymer and the concentration of polymer. Different proportion of HPMC was associated with decrease in the overall cumulative drug release rate. The initial burst release of Isoniazid was decreased by higher viscosity grade polymer. Thus, we conclude that from among all the developed formulations, F1 formulation sustained the drug release for longer period of time over 12 h when compared to other formulations. So, F1 was selected as best formulation and fulfills all the requirements for sustained release.