Please send correspondence to: Kenneth E. Schmader, MD, 182 GRECC, 508 Fulton St., Durham VA Medical Center, Durham, NC 27705; phone: 919-286-6932; fax: 919-286-6832 Author Contributions: Kenneth E. Schmader: study concept and design, acquisition of subjects and data, interpretation of data, and preparation of manuscript; Gary R. Johnson: study concept and design, acquisition of data, analysis and interpretation of data, and preparation of manuscript; Patricia Saddier: study concept and design, interpretation of data, and preparation of manuscript; Maria Ciarleglio: study design, analysis and interpretation of data, and preparation of manuscript; William W.B. Wang: study design, analysis and interpretation of data, and preparation of manuscript; Jane H. Zhang: study design, analysis and interpretation of data, and preparation of manuscript; Ivan S.F. Chan: study design, analysis and interpretation of data, and preparation of manuscript; Shing-Shing Yeh: study design, acquisition of subjects and data, interpretation of data, and preparation of manuscript; Myron J. Levin: study concept and design, acquisition of subjects and data, interpretation of data, and preparation of manuscript; Ruth M. Harbecke: interpretation of data, and preparation of manuscript; Michael N. Oxman: study concept and design, acquisition of subjects and data, interpretation of data, and preparation of manuscript. All authors approved the final version. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptObjective-To determine the efficacy of a zoster vaccine on herpes zoster related interference with activities of daily living (ADL) and health-related quality of life (HRQL).Design-Randomized double-blind placebo controlled trial. Setting-22 US sites.Patients-38,546 women and men ≥60 years of age. Intervention-Zoster vaccine or placebo.Measurements-Herpes zoster Burden of Interference with ADL and HRQL using ratings from the Zoster Brief Pain Inventory and SF-12 Mental and Physical Component Scores. Vaccine efficacy was calculated for the modified-intention-to-treat trial population and solely among those subjects who developed herpes zoster.Results-For the modified-intention-to-treat population, the overall zoster vaccine efficacy was 66% (95% CI: 55, 74) for Zoster Brief Pain Inventory ADL Burden of Interference Score and 55% (95% CI: 48, 61) for both the SF-12 Mental and Physical Component Scores. Among subjects who developed herpes zoster, zoster vaccine reduced the Zoster Brief Pain Inventory ADL Burden of Interference Score by 31% (95% CI: 12, 51) respectively, and did not significantly reduce the impact on HRQL.Conclusions-Zoster vaccine reduced the burden of herpes zoster related interference with ADL in the population of vaccinees and among vaccinees who developed herpes zoster. Zoster vaccine reduced the impact of herpes zoster on HRQL in the population of vaccinees but not among vaccinees who developed herpes zoster.