The objective of this study was to design oral sustained release matrix tablets of lamivudine using hydroxyl propyl methyl cellulose and ethyl cellulose as retardant polymers and to study the effect of various mixtures of drug and polymers on the release profile of the formulation. In vitro release studies were performed using ELECTROLAB TDT 08L 8 basket dissolution apparatus in 900(ml) of pH 6.8 phosphate buffer at 100rpm. The release kinetics were analyzed using zeroorder, Higuchi’s equation and Korsmeyer-Peppas equation. The in-vitro kinetic data is subjected to log time-log drug release transformation plot (Korsmeyer-Peppas plot),all the slope values ranges from 1.020803 to 1.116491(n>1) revealed the fact that the drug release follows super case II transport diffusion , possibly owing to chain distanglement and swelling of hydrophilic polymer. The formulations were also subjected to FT-IR compatibility study by mixing the physical mixtures of lamivudine and polymers in various ratios. The obtained FT-IR spectra revealed that there is no major compatibility issues with the physical mixtures. The in vitro studies revealed that the formulation F7 can be taken as an ideal or optimized formulation of sustained release tablets for 16 hours release as it fulfills all the requirements for sustained release tablet.