Method: The study was conducted at an integrated healthcare organization. The vaccinated cohort consisted of the organization members who were vaccinated against herpes zoster (HZ) between 01-JAN-2007 and 31-DEC-2014 at the age of less than or equal to 60 years. The unvaccinated cohort study consisted of randomly sampled members who were matched at a randomly sampled members who were matched at a ratio of 3:1 to the vaccinated cohort with respect to sex, age and length. Since HZ vaccine is not recommended for immune-compromised patients, we excluded any members who had indication of being immunocompromised as of the index date, to make the vaccinated and unvaccinated cohorts more comparable in terms of underlying herpes zoster risk; furthermore, any reduced risk associated with HZ vaccine could be interpretable in the context of national recommendations. As in our previous study, we classified any member who received a diagnosis of human immunodeficiency virus infection, leukemia, or lymphoma or a prescription for immunosuppressing agents within 1 year before the index date as immunocompromised. Statistical Analysis: The overall incidence of HZ was calculated by dividing the number of HZ cases by the total number of person-years. The cumulative risk of HZ was estimated by the Kaplan-Meier method, and the difference between the vaccinated and the unvaccinated cumulative risk estimates was tested by the log-rank test. Adjusted hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression models adjusted for age, sex, race/ethnicity, healthcare utilization, length of membership prior to the index date, and chronic comorbid diseases. Vaccine effectiveness by follow-up year after vaccination was estimated as 1 - adjusted HR, using data from the vaccinated and the unvaccinated cohorts at risk for HZ at the start of each year following vaccination. To evaluate the impact of possible differential censoring and HZ risk after follow-up between the vaccinated and unvaccinated cohorts. Results: There were 176078 vaccinated and 528234 unvaccinated persons included in the study. Compared with the unvaccinated cohort persons in the vaccinated cohort to have had a larger number of outpatient visits but had fewer emergency department visits and hospitalizations in the 12 months before the index date. The vaccinated cohort has a lower prevalence of chronic diseases. The number of HZ cases was 5239 in 653734 person- years (8.0 cases/1000 person-years; 95% CI, 7.8-8.2 cases/1000 person years) among vaccinated persons and 20181 in 1400716 person-years (14.4 cases/1000 person-years; 95% CI, 14.2-14.6 cases/1000 person-years) among unvaccinated persons. The HZ incidence rate ratio, comparing the HR among vaccinated persons to that for unvaccinated individuals, was 0.56. In the adjusted analysis, vaccination was associated with a reduced risk of herpes zoster (HR, 0.51; 95% CI, .49-.52); this reduction occurred in all age strata and among those with chronic diseases. The adjusted HR increased from 0.44 (95% CI, .41-47) for the group aged 60-64 years to 0.58 (95% CI, .53-64) for the group aged >80 years. This decreasing pattern was similar. This decreasing pattern was similar between the younger group (aged 60-69 years) and the older group (aged >70 years). The 8-year cumulative risk of HZ in the vaccinated and the unvaccinated groups was 7.07% and 10.54%, respectively (P<.05). The sensitivity analyses showed that the pattern of decreasing effectiveness remained qualitatively unchanged, although the magnitude of the decline was not as large as that in the overall cohort. This literature marketed report as received from healthcare professional regarding 5239 patients of unknown age and gender. On an unknown dates, the patient was vaccinated with ZOSTAVAX. On an unknown dates, the patients experience herpes zoster despite vaccination. The outcome of the events was unknown. The reporter considered events to be related to ZOSTAVAX. Additional information has been requested.