In the present investigation, an attempt was made to formulate and characterize the oral sustained release monolithic matrix tablets of Zidovudine order to improve efficacy, reduce the frequency of administration and better patient compliance. Monolithic Matrix tablets of Zidovudine were formulated using different concentrations of hydrophilic polymers such as HPMCK4M, xanthum gum, and carrageenan gum. The powder blend was evaluated for pre compression properties. The sustained release matrix tablets were prepared by Wet granulation method. The tablets were evaluated for thickness, weight variation test, hardness, friability, and drug content and they were further evaluated for the in-vitro release of drug over a period of 12 hours. The drug release from optimized formulation F10 followed zero-order kinetics via non-Fickian (anomalous) diffusion. FTIR studies revealed that there was no interaction between the drug and excipients. In conclusion, the results indicated that the prepared sustained-release monolithic matrix tablets of Zidovudine could perform therapeutically better than conventional tablets with improved efficacy and better patient compliance.