The study evaluated the efficacy and safety of an adjuvanted herpes zoster subunit vaccine (HZ/su) in older adults (≥50 years) across 18 countries. A total of 15,411 participants were randomized to receive either two doses of HZ/su or placebo, with a mean follow-up of 3.2 years. The primary outcome was the reduction in the risk of herpes zoster. The overall vaccine efficacy was 97.2% (95% CI, 93.7 to 99.0; P<0.001), with similar efficacy across all age groups (96.6% to 97.9%). Solicited injection-site and systemic reactions were more frequent in the HZ/su group, but serious adverse events and potential immune-mediated diseases were similar between the groups. The HZ/su vaccine significantly reduced the risk of herpes zoster in older adults, with no significant safety concerns identified.The study evaluated the efficacy and safety of an adjuvanted herpes zoster subunit vaccine (HZ/su) in older adults (≥50 years) across 18 countries. A total of 15,411 participants were randomized to receive either two doses of HZ/su or placebo, with a mean follow-up of 3.2 years. The primary outcome was the reduction in the risk of herpes zoster. The overall vaccine efficacy was 97.2% (95% CI, 93.7 to 99.0; P<0.001), with similar efficacy across all age groups (96.6% to 97.9%). Solicited injection-site and systemic reactions were more frequent in the HZ/su group, but serious adverse events and potential immune-mediated diseases were similar between the groups. The HZ/su vaccine significantly reduced the risk of herpes zoster in older adults, with no significant safety concerns identified.