Varicella-zoster virus (VZV) reactivation is a relatively common cause of morbidity following autologous hematopoietic cell transplant (auto-HCT). The Centers for Disease Control in 2009 recommended extending VZV prophylaxis for 1 year post-transplantation. We retrospectively analyzed rates of VZV reactivation following auto-HCT at our transplant center prior to and after the implementation of extended antiviral prophylaxis in June 2008. The study population was divided into three different cohorts according to the length of VZV prophylaxis as following: (1) prophylaxis until neutrophil recovery to ≥500/μL (n = 77), (2) prophylaxis for 6 months (n = 12), or (3) 12 months (n = 40) post-auto-HCT. All patients received acyclovir 400 mg oral or intravenously twice daily or valacyclovir 500 mg oral daily. For patients in whom VZV reactivation occurred, data was collected on severity of infection, time of onset, treatment, and any associated complications. One hundred twenty-nine patients undergoing auto-HCT between January 1, 2004 and January 31, 2010 were included in the study. There was a significant difference in the rates of VZV reactivation between the neutrophil recovery and 12 months prophylaxis cohorts at 14 % (n = 11) and 2 % (n = 1) (P = 0.04), respectively. VZV reactivation rate in the 6-month prophylaxis group was 17 % (n = 2), but did not reach statistical significance due to small numbers. In the subset of auto-HCT patients treated with bortezomib, 13 % (n = 2) developed VZV reactivation in the neutrophil recovery group, while no events occurred in the other two cohorts. Complications of VZV reactivation include post-herpetic neuralgia (n = 5), severe pain (n = 3), scarring (n = 1), and motor weakness (n = 1); two patients required hospitalization and three patients developed disseminated zoster. Our limited retrospective analysis suggests a significant reduction in rates of post-auto-HCT rates of VZV reactivation with extended 12 months antiviral prophylaxis. VZV reactivation is a significant complication post-auto-HCT, and extended prophylaxis appears to be safe and effective in this setting.