Genital herpes is a common, highly infectious, contagious disease caused by a virus that infects genital areas. Oral and topical acyclovir formulations are available in the market but its bioavailability is reported to be 10 to 20%, hence there is a need to develop vaginal drug delivery. Vaginal tablets of acyclovir were prepared by direct compression method using carbopol 934P and xanthan gum as bioadhesive polymers. The effect of process variables, amount of carbopol 934P, xanthan gum and sodium bicarbonate on the responses percent swelling index and percent drug release were studied using D-Optimal design. Parameters like swelling index, surface pH, In-vitro drug release, In-vitro drug permeation and bioadhesion strength were studied. The vaginal tablets were found to sustain the release of acyclovir for 12 hrs in simulated vaginal fluid. The maximum bioadhesion strength was observed in the tablets formulated with increased concentration of xanthan gum. The possible drug release mechanism for the optimized vaginal tablet of acyclovir was observed to be Korsemeyer - Peppas. Invitro absorption studies showed that the drug absorption is low and the amount of the drug in the absorption medium at the end of 8th hour was found to be 26.03%. Stability studies indicated that there were no significant changes in drug content for period of 6 months. Thus stable safe vaginal tablets of acyclovir can be formulated to impose maximum bioavailability of drug, by sustaining the drug delivery thereby improving the patient compliance.