Aim: The diagnosis of metabolic dysfunction-associated steatotic liver disease (MASLD) relies mostly on active screening procedures. Risk scores are useful to identify patients at-higher risk for fibrosis. The Fibrosis-4 score (FIB-4) is the most widely used. It includes age, AST, ALT, and platelet count. Most guidelines, including Italian guidelines, recommend elastographic assessment in all subjects with FIB-4 scores above 1.3. To verify the prevalence of positive Fibrosis-4 (FIB-4) score, a screening test for metabolic-associated liver disease, in a large population-based sample in the Tuscany Italian Region, and to identify sub-populations at higher risk which could be targeted by specific screening programs. Methods: A Population-based survey was performed in the Italian region of Tuscany, with Tuscany health informative system’s administrative data. Results: The population living in the included areas, after excluding individuals with liver disease, was composed by 594,923 individuals (Tab. 1); of those, 8.38% were affected by diabetes, 2.9% had dyslipidemia, and 22.9% were aged 70 years or more. FIB-4 score was available in 182.548 (32%) subjects. The proportion of subjects with FIB-4 >1.3, among those with available FIB-4, was 41.6% (95%CI, 41.4%-41.8%), representing 12.8% (95%CI, 12.7%-12.8%) of the whole population. Among subjects aged 70 years or over, 38.4% (95%CI, 38.2%-38.7%) of the whole sample and 74.9% (95%CI 74.6%-75.3%) of those with available data, had FIB-4 >1.3 (Tab. 1); when applying a FIB-4 threshold of 2 in those aged 70 years or over, 22,624 subjects had a positive result, corresponding 16.6% (95%CI, 16.4%-16.8%) of the population, and 32.3% (95%CI, 32.0%-32.7%) of those with available data. If we apply a 1.3 FIB-4 threshold for those aged less than 70 year, and a threshold of 2 for those of 70 years or over, the prevalence of positive subjects in the whole sample would be 7.8% (95%CI, 7.7%-7.8%), and 25.3% (95%CI, 25.1%-25.5%) of those with available data. Conclusions: The relevant proportion of FIB-4 positivity in the general population poses a significant burden for further screening with liver elastography. Targeting people with diabetes and/or adopting a FIB-4 threshold of 2 in those aged more than 70 years could increase the cost-effectiveness of the screening procedures.