Varicella zoster virus (VZV)-related disease, particularly herpes zoster, is a complication of organ transplantation due to long-term immunosuppression. We determined the incidence and risk factors for post-transplant VZV infection by retrospectively reviewing the medical records of a cohort of 612 adult renal transplant recipients transplanted at Mayo Clinic Rochester between October 1, 2001 and October 1, 2004. Thirty-seven subjects developed herpes zoster, corresponding to a follow-up time-adjusted incidence of 11.2% at 4 years post transplant. The incidence rate of zoster was relatively constant between 6 months and 4 years, yielding an average incidence of approximately 28 per 1000 person-years. The risk of developing post-transplant zoster increased with increasing age at transplant, with each decade conferring a 1.42-fold (P=0.009) increase in risk of zoster development. Seronegativity at time of transplant conferred over 3 times the risk of development of post-transplant zoster (hazard ratio 3.4; P=0.04) compared with seropositivity. Adult kidney transplant recipients are at high risk for the development of post-transplant zoster.