Limited data are available on prophylaxis for herpes simplex virus (HSV) and varicella zoster virus (VZV) disease following autologous hematopoietic stem cell transplantation (auto-HCT). We retrospectively reviewed the clinical charts of 105 consecutive patients who underwent their first auto-HCT at our institution between September 2007 and June 2014. Before August 2009, 30 patients received oral acyclovir at 1000 mg/day until engraftment, whereas after September 2009, 69 patients received oral acyclovir at 200 mg/day. After engraftment, acyclovir was continued at 200 mg/day at the discretion of the attending physicians in both groups. The cumulative incidence of HSV disease at 1 year after auto-HCT was 7.7 and 4.5 % in patients who received oral acyclovir at 1000 and 200 mg/day, respectively (P = 0.75). Patients were next divided into three groups according to the timing at which acyclovir prophylaxis was stopped after auto-HCT; at engraftment, between engraftment and 1 year after auto-HCT, and later than 1 year. The cumulative incidence of VZV disease was 25.8, 7.7, and 0.0 % at 1 year, respectively. This study suggests that low-dose acyclovir prophylaxis may be effective for preventing HSV and VZV disease after auto-HCT. Our findings support the recommendation of acyclovir prophylaxis within the first year after auto-HCT.