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This study aimed to: (1) estimate the disease burden of herpes zoster (HZ) and (2) assess the potential public health impact of introducing adjuvanted recombinant zoster vaccine (RZV) compared with no vaccination in adults aged ≥50 years in Argentina, Brazil, Mexico, Chile, and Colombia using the ZOster ecoNomic Analysis (ZONA) static multicohort Markov model. The model followed individuals aged ≥50 years from administration of RZV over their remaining lifetime. Inputs were based, most often, on local data. First dose coverage was assumed to be 35%, with 75% second dose compliance. It was predicted that without RZV, there would be 23,558,675 HZ cases, 6,115,981 post-herpetic neuralgia (PHN) cases, and 7,058,779 non-PHN complications in the five countries, but introducing RZV under assumed coverage could avoid 4,583,787 (19%) HZ cases, 1,130,751 (18%) PHN cases, and 1,373,419 (19%) non-PHN complications. Also, 10427,504 (20%) doctor’s office visits and 1,630,201 (19%) days of hospitalization could be averted in the three countries (Argentina, Brazil, and Mexico) with available input data. The numbers needed to be vaccinated to avoid one case of HZ were 9–10 across countries, and to avoid one case of PHN, 35–40. One-way sensitivity analyses showed that the input parameters with the largest impact on the estimated number of HZ cases avoided were first dose coverage, initial HZ incidence, and vaccine efficacy waning. In conclusion, the introduction of RZV for older adults in Latin America could greatly reduce the public health burden of HZ and reduce the related doctor visits and hospitalization days.