This randomized, double-blind, parallel-group study compared the efficacy and safety of famciclovir administered at 250 mg thrice daily with acyclovir 800 mg 5 times daily for the treatment of acute uncomplicated herpes zoster in immunocompetent adults. A total of 55 patients participated in this trial. Twenty seven patients (49.1%) were randomized into the famciclovir plus placebo treatment group and 28 (50.9%) into the acyclovir plus placebo group. Six of the 55 patients did not complete the study. Two of these patients were in the famciclovir plus placebo group and dropped out due to deviation from the study protocol. Four patients in the acyclovir plus placebo group did not complete the study protocol due to adverse events (n = 2), deviation from the protocol (n = 1), or loss to follow-up (n = 1). Treatment was initiated within 72 h of onset of the zoster rash and was continued for 7 days. When treatment was initiated within 72 h, famciclovir was as effective as acyclovir for healing the cutaneous lesion, as indicated by the time to full crusting, loss of acute phase pain, loss of vesicles, and loss of crusts. Famciclovir was well tolerated and had a more favorable adverse event profile compared to acyclovir. Constipation, hematuria, and glycosuria were the most commonly reported adverse events, but only constipation was considered to have a possible relationship to the treatment. In conclusion, famciclovir, administered less frequently and at lower unit doses than acyclovir, is an effective treatment for uncomplicated herpes zoster.