Herpes zoster (HZ) is a common disease characterized by the recurrence of varicella zoster, that stays dormant in sensory ganglia. The primary goal of this study was to compare efficiencies of famciclovir, valaciclovir, and brivudine in terms of pain relief in HZ patients. Records of patients who were admitted to the Dermatology Clinic of our hospital due to acute HZ between the years 2012 and 2014 were retrospectively analyzed. Treatment decisions were at the discretion of caring physicians as valaciclovir (VACV), famciclovir (FCV), and brivudine (BRV) based on the clinical observations. BRV, FCV, and VACV were effective in treating pain in acute HZ. There was no significant difference between mild and moderate HZ patients. In severe cases, a significant reduction in intensity of pain was observed on day 3 in the BRV group, on day 7 in the FCV group, and at 2–3 weeks in the VACV group. There were no significant side effects observed in any of the groups. Results of this study indicate that brivudine may be the first choice in severe HZ cases as it controls pain earlier and is easier to use because of its once daily administration.