Background: Acyclovir, a specific and selective inhibitor of replication of herpesviridae family, has well documented efficacy for speedy rash healing and decreasing pain of herpes zoster. Limited oral bioavailability of acyclovir requires frequent dosing. Valacyclovir is rapidly and almost completely converted to acyclovir in vivo and gives three to fivefold increase in acyclovir bioavailability. The aim of this study was to assess the clinical efficacy, safety and tolerability of oral valacyclovir versus standard oral acyclovir in the treatment of herpes zoster. Methods: A blind randomized prospective study was performed during May 2007 to August 2007 in Midnapore Medical College. Immunocompetent patients, aged ≥40yrs presenting with herpes zoster within 72 hours after onset of rash were enrolled and randomized to receive one of the following treatments: 1000 mg of valacyclovir thrice daily for 7 days or acyclovir 800 mg 5 times daily for 7 days. A total of 60 patients were included and randomized to receive either valacyclovir (n=30) or acyclovir (n=30) and they were evaluated at 8 days, 15 days and 29 days, respectively. Results: A statistically significant reduction of skin lesion and zoster associated pain were noticed in valacyclovir compared to acyclovir group. However, presence of post herpetic neuralgia on the 29th day was less in acyclovir compared to valacyclovir group (70.0% vs. 83.3%, P>0.05). Only one patient on valacyclovir and two patients on acyclovir complained of nausea and mild abdominal pain. Conclusion: We conclude that for the management of herpes zoster, valacyclovir might be superior to acyclovir in respect to reduction of skin lesions and pain.