ObjectiveOur study's objective was to assess the incidence trends and healthcare resource utilization of hospitalizations for Tick-Borne Encephalitis (TBE) and associated costs in Italy in order to improve public awareness and preventive measures. MethodsThis retrospective observational study was based on the Italian Ministry of Health's Hospital Discharge Record (HDR) database. Data were gathered across Italy from 2015 to 2019, selecting hospitalizations with ICD-9 code 063 related to TBE, both in primary and secondary diagnoses. For each year, we collected the following variables: number of hospitalizations, hospitalization rate, mortality rate, mean length of hospital stay, hospital ward, and cost of hospitalization. ResultsThere were a total of 237 hospitalizations from 2015 to 2019; 62 % of those were male. The lowest number of TBE hospitalizations was in 2015 (21 cases, corresponding to 0.35 per million inhabitants), the highest in 2019 (64 cases, 1.04 per million inhabitants). The summer months saw a greater than average number of hospitalizations. For the years analyzed, the cumulative number of cases peaked in June (54 cases), July (46 cases), and August (35 cases). There were only two deaths registered in our study sample. TBE cases were mostly localized in the North-Eastern regions of Italy. TBE incidence during the study period in the most affected areas were: Autonomous Province of Trento, ranging from 11.2 to 42.3 per million inhabitants, Autonomous Province of South Tyrol, from 0 to 21.1 per million inhabitants, and Veneto Region, from 2.6 to 4.5 per million inhabitants. In the study period, the average length of hospital stay was largely stable ranging from 10.6 days to 12.8 days, with related costs ranging from 5,813.7 € to 7,352.5 €. ConclusionsAccording to our data, the majority of TBE hospitalizations occur in North-East Italy with an increasing trend over the analyzed period. Even though Italy has fewer TBE cases than other neighboring European countries, the health and economic impact can be high in the affected areas.