Herpes zoster (HZ) is the painful reactivation of latent varicella zoster virus infection. The incidence of HZ may be increased in some autoimmune diseases, including systemic lupus erythematosus (SLE). We examined the incidence and risk factors for HZ in a prospective cohort of patients with physician-diagnosed SLE compared to those diagnosed with non-inflammatory musculoskeletal conditions (MSK). After excluding participants with a history of prior HZ at enrollment, we followed 1485 SLE patients and 2775 MSK with semi-annual mailed questionnaires for incident HZ between 2001 and 2010. Age-adjusted incidences were calculated for each group and Cox proportional hazard models were used to identify predictors of HZ. Zostavax® vaccination rates were compared between groups. Participants had a mean age of 60 years at enrollment, with 13.9 years of disease. SLE patients had more HZ at all ages, with an age-adjusted incidence of 12.0/1000 person-years compared to MSK (8.7/1000 person-years) and a hazard ratio of 1.7 (95% CI 1.08-2.71) for SLE. Increasing age and reduced functional status were independent predictors of HZ. In SLE, prednisone and mycophenolate mofetil use conferred additional risk. SLE had the lowest HZ vaccination rates among age-eligible subjects.