OBJECTIVES: Herpes Zoster (HZ) is a painful skin rash that occurs most frequently among the elderly. A vaccine has recently been licensed in Europe to prevent HZ in individuals aged ≥50 years. As of today, the actual annual waning-rate (WR) of vaccine-induced-immunity (VI) is unknown. To investigate the impact of different WRs on the incremental-cost-effectiveness-ratio (ICER) at different ages at vaccination, we performed a health economic analysis for the German statutory-health-insurance setting. METHODS: Based on a Markov-model, we compared a HZ-vaccination-strategy to a scenario without vaccination in Germany targeting different cohorts to identify the most efficient age at vaccination (50, 60, or 70 years). A societal-perspective (SP) was considered, country- and age-specific demographic, epidemiological, and cost-of-illness input-data were utilized. We assumed a vaccine-price of 140.48 Euro/dose and 10 year stable VI. Thereafter an exponential waning of VI based on several annual relative WR (0, 2.5, 5, 7.5, 10 and 50%) was assumed. All monetary amounts were in Euro 2010. The cycle-length was a quarter; we considered a lifelong time-horizon. The discount-rate was 3% for outcomes and costs. Results were presented as costs/quality-adjusted life-year (QALY) gained ICERs. RESULTS: With annual WR <5% ICERs increase with age at vaccination from 50 (0% WR: 16,567€/QALY gained) to 70 years (0% WR: 37,285€/QALY gained). When WR is ≥5% the vaccination-age-specific ICERs become U-shaped with the minimum ICERs at 60 years (5% WR: 25,474€/QALY gained). With high annual WR (50%) the ICERs at vaccination-age 70 (50,847€/QALY) are lower than ICERs at 50 years (56,871€/QALY). CONCLUSIONS: The annual WR has a high impact on vaccination-age-specific ICERs. To obtain lowest ICERs, HZ-vaccine should be given early in life (e.g. 50 years) if WR is low. When annual WR is >4%, the most efficient age at vaccination is 60 years. Evidence on the actual WR after HZ-vaccination has yet to be established.