HZ infection is a common complication following hematopoietic stem cell transplantation (HSCT). We reviewed the incidence, complications, and associated risk factors in a post-HSCT pediatric population at a single center and examined whether antecedent blood counts or transaminase levels (AST, ALT) might predict the onset of infection prior to the development of skin manifestations. Seventy-eight children between the ages of 2 months and 21 years developed HZ among the 309 patients, on whom data was available, who underwent HSCT from January 1995 to December 2002. Underlying diagnoses included: acute leukemia (n=108), chronic myelogenous leukemia (n=22), myelodysplastic syndrome (n=24) and other conditions (n=155). Two hundred patients underwent an allogeneic HSCT (98 sibling donor, 102 unrelated donor) and 109 underwent an autologous HSCT. The incidence of HZ was 25% by 10 months and 40% by 70 months post-HSCT. Post-herpetic neuralgia occurred in 21/73 (29%; 95% CI=19%, 41%) evaluable patients, disseminated skin involvement in 15/74 (20%; 95% CI= 12%, 31%) patients and visceral organ involvement in 6/75 (8%; 95% CI= 3%, 17%) patients. Acyclovir prophylaxis for cytomegalovirus (CMV) antigen positivity was given for 21 days post-BMT in 49/75 (65%) patients and had no impact on the incidence or onset of HZ, nor did immune compromise (defined as history of chemotherapy or underlying primary immune deficiency) prior to HSCT. Risk factors for development of HZ included: patient age-greater than 10 years (p<0.0001), allogeneic HSCT (p<0.001), and conditioning with total body irradiation (TBI) (p<0.059). Type of allogeneic donor did not add significantly to the model. Graft-versus-host-disease (GVHD) increased the interval to HZ infection (p<0.0018). There was insufficient evidence to attribute this surprising result to CMV prophylaxis. However, prior GVHD did increase the risk of disseminated skin involvement (p<0.016). There was a significant change in ALT level in the month preceding diagnosis of HZ (p<0.02), with 22/37 (59%) evaluable patients having a progressive increase. This rise in ALT level was not associated with GVHD (p=0.60). Changes in AST levels, white blood cell and platelet counts were not significant. Forty-four patients were admitted to hospital for HZ infection for a median of 6 days (range 2–39). Length of stay for allogeneic patients was significantly affected by skin dissemination and visceral involvement (p<0.023 and p<0.034, respectively) and not by donor type, prior immune status, GVHD or TBI. Inclusion of HZ infection post-HSCT in the differential diagnosis of patients with a rising ALT level, particularly if > 10 years of age after allogeneic HSCT with TBI conditioning may allow for earlier initiation of therapy with less morbidity and decreased need for hospital admission.