Rotavirus is considered the main cause of severe gastroenteritis and nosocomial infections in Pediatric units, especially during late winter and early spring season in temperate region. In 2013 Sicilian Region, for the first time in Italy, introduced universal Rotavirus vaccination. This study aims to estimate health and economic impact on rotavirus Gastroenteritis (RVGE) among children aged 0–59 months in Sicily, after rotavirus vaccine introduction.We analyzed hospital discharge records including a diagnosis of RVGE occurred from 1st January 2009 to 31st December 2016 among hospitalized children aged 0 to 59 months, residents in Sicily. RVGEs were defined as all hospitalizations with an ICD-9-CM diagnosis code of 008.61 on first or any diagnosis position. Also an economic impact analysis on Health Regional System was conducted.We observed a consistent decline of hospitalization after rotavirus vaccination introduction from 394 per 100,000 in 2009–2012 to 220 per 100,000 in 2013–2016. We found a change in the peak of reported cases by at least one month from March-April in the pre-vaccination period to May-June in the post-vaccination period. Since 2013, we estimated that the annual average cost saved is 1,134,056 € when considering direct and indirect costs to health care as well as vaccination costs.Our study is the first analysis conducted as far as we are aware in a high-income setting with poor coverage (lower than 50%), demonstrating a significant reduction of RVGE hospitalizations in Sicily after vaccine introduction. Moreover, was observed a consistent impact of vaccination on health care cost saving.