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C Azzari,1 V Baldo,2 S Giuffrida,3 R Gani,4 E O’Brien,5 C Alimenti,6 VJ Daniels,7 LJ Wolfson7 1Department of Health Sciences, University of Florence and Meyer Children’s University Hospital, Florence 50139, Italy; 2Hygiene and Public Health Unit Department of Cardiac Thoracic Vascular Sciences and Public Health University of Padua, Padua 35100, Italy; 3LHU Reggio Calabria, Reggio 89100, Calabria, Italy; 4Evidence Synthesis, Modeling & Communication, Evidera, London, UK; 5Evidence Synthesis, Modeling & Communication, Evidera, San Francisco, CA, USA; 6MSD Italy, Market Access, Roma, Italy; 7Center for Observational and Real-World Evidence, Merck & Co., Inc., Kenilworth, NJ, USACorrespondence: LJ WolfsonMerck & Co., Inc., Center for Observational and Real-World Evidence (CORE), 600 Corporate Drive, CRB-205, Kenilworth, NJ 08833, USATel +1 267-305-0650Email lara.wolfson@merck.comBackground: In 2017, varicella vaccination became mandatory for all children in Italy, based on a two-dose schedule administered at 12– 15 months of age and 5 to 6 years of age. Varicella vaccines are available in different formulations (as a single vaccine or as a combination vaccine together with measles, mumps, and rubella) and are made by multiple manufacturers with different effectiveness profiles. This study calculates the cost-effectiveness of a range of varicella vaccination strategies to identify the optimal strategy for Italy.Methods: A dynamic transmission cost-effectiveness model was applied in Italy to simulate the long-term (50 years) costs and outcomes associated with different varicella vaccination strategies. Five vaccination strategies were evaluated using the model: two doses of two different combination Measles-Mumps-Rubella-Varicella vaccines (either Vaccine A (MSD) [denoted QQVa] or Vaccine B (GSK) [denoted QQVb]); a first dose of a single Varicella vaccine followed by a second dose of a combination vaccine (either Vaccine C (MSD) followed by Vaccine A [denoted MQVa] or Vaccine D (GSK) followed by Vaccine B [denoted MQVb]); or no vaccine at all (NV). The model was adapted for Italy using publicly available Italian data and expert opinion.Results: Over the 50-year time-horizon, in the absence of universal varicella vaccination, there would be 34.8 million varicella cases, 142 varicella-infection-related deaths, and € 23 billion in societal costs. The cost per capita from a societal perspective ranged from € 164.55 to € 392.18 with NV being the most expensive and QQVa the least expensive. The most effective strategy was QQVa, which resulted in a 66% decrease in varicella cases and 30% reduction in varicella-related deaths compared to NV strategy. QQVa led to a net saving in societal cost around € 13 billion compared to NV as the cost of vaccination was more than offset by the savings that resulted from the reduced burden of illness.Conclusion: Varicella vaccination has a major impact on reducing varicella incidence, prevalence, and societal costs. This analysis supports the policy for universal varicella vaccination in Italy as the NV strategy was the most expensive and resulted in the poorest outcomes. QQVa offers the greatest benefits at the lowest cost and should be considered as a potential priority strategy for Italian population.Keywords: varicella, vaccination, Italy, health-economics, cost-effectiveness, chickenpox, MMRV, varicella zoster virus