Varicella-zoster virus infections have increased globally, with complications such as postherpetic neuralgia and neurological sequelae. The recombinant vaccine against herpes zoster is proposed as a preventive strategy. This systematic review evaluates its effectiveness and safety in healthy and high-risk populations. A systematic review of randomized controlled trials comparing the effectiveness and safety of the vaccine was conducted. The search was carried out in Epistemonikos. Two researchers independently assessed the eligibility of the studies and the risk of bias was evaluated using the Cochrane Risk of Bias 2 tool. A meta-analysis of homogeneous results was conducted, and the certainty of the evidence was evaluated using GRADE. A minimally contextualized approach was adopted using predetermined thresholds. Nine randomized controlled trials were selected. The vaccine demonstrated a significant reduction in the incidence of herpes zoster in high-risk populations (risk difference of 140 fewer per 1000) with high certainty. However, in healthy populations, the effect was trivial (28 fewer per 1000). No significant differences were observed in postherpetic neuralgia in any of the populations analyzed. Adverse events increased in both populations, though no discrepancies in serious adverse events were noted. In high-risk populations, where the incidence of herpes zoster and its complications is higher, the vaccine demonstrated effectiveness in lowering the incidence of the disease, though not in that of postherpetic neuralgia. Conversely, in healthy populations, the impact of the vaccine was trivial. Individualized and informed recommendations are crucial when considering this vaccine.
