OBJECTIVE: The objective of this study was to compare the efficacy and safety of Valacyclovir and Famcyclovir in the management of Acute Herpes Zoster. MATERIALS AND METHODS: Relevant data were taken from 162 patients with herpes zoster who presented within 72 hours of onset of rash and were randomized into 2 groups of 81 each. The 1st group received Valacyclovir 1gm thrice a day for 7 days while those in the 2nd group received Famcyclovir 500 mg thrice a day for 7 days respectively and evaluated at the end of each week upto 6 weeks period and examined for full crusting of lesions, complete healing of the lesion and loss of acute pain (visual analogue scale scores for pain). Safety assessment was based on adverse effects. RESULTS: The intent to treat analysis (162 Pts) showed that valacyclovir for 7 days significantly accelerated the resolution of pain in Herpes zoster pts (P=0.00014) compared with famcyclovir; median pain duration were 21 and 22 days respectively. There was no difference between treatments in time taken for healing of lesions. Adverse effects like nausea, vomiting, diarrhoea and headache were commonly reported in both groups. Valacyclovir was found to be statistically superior over Famcyclovir in terms of G.I adverse effects. Compliance was also better with Valacyclovir. CONCLUSION: Oral Valacyclovir administered three times daily for 7 days during acute zoster infection offers significant benefit by providing a well-tolerated, cost effective and accelerated rate of resolution of pain and maintains the favorable safety profile compared to oral Famcyclovir.