The aim of the present study was to prepare and characterize controlled-release matrix tablets of zidovudine using hydrophilic HPMC K4 M or Carbopol 934 alone or in combination with hydrophobic ethyl cellulose. Release kinetics was evaluated by using USP XXIV dissolution apparatus No.2 (paddle) type. Scanning electron microscopy was used to visualize the effect of dissolution medium on matrix tablet surface. The in vitro results of controlled - release zidovudine tablets were compared with conventional marketed tablet Zidovir. The in vitro drug release study revealed that HPMC K4 M or Carbopol 934 preparation was able to sustain the drug release near to 6 hours. Combining HPMC K4 M or Carbopol 934 with ethyl cellulose sustained the drug release for nearly 12 h. The in vitro evaluation showed that the drug release may be by diffusion along with erosion. Results suggest that the developed controlled-release tablets of zidovudine could perform therapeutically better than marketed dosage forms, leading to improve efficacy, controlling the release and better patient compliance.