In the current study, the influence of chitosan on the dissolution rate and bioavailability of acyclovir has been illustrated through the preparation of co-crystals by simple solvent change method. Chitosan was precipitated on acyclovir crystals using sodium citrate as the salting out agent. The pure drug and the prepared co-crystals using different concentrations and molecular weights of chitosan were characterized in terms of drug content, particle size, thermal behavior, IR analysis, surface morphology, in vitro drug release and physical stability. The results obtained showed that the practical yield of the prepared co-crystals was found to be inversely proportional to chitosan concentration. The drug content of the co-crystals was uniform among the different batches. The prepared co-crystals showed a slower drug release when compared to that of pure drug. The considerable change in the dissolution rate of acyclovir from optimized crystal formulation was attributed to the wetting effect of chitosan, the reduction in drug crystallinity and the altered surface morphology. The thermograms showed a decrease in the melting enthalpy of acyclovir indicating a disorder in the crystalline content whereas IR spectroscopy studies revealed an interaction between acyclovir and chitosan. The optimized co-crystals were stable for three months at 40°C and 75 ± 5% RH.