OBJECTIVES: Three projects have been implemented to gather the Real World Data (RWD) required to answer to National and Regional decision maker’s need of estimating the impact of the introduction of PCSK9 inhibitors on the Italian National Healthcare Service at reimbursement time. METHODS:  RWD on PCSK9 eligible patients were collected via thee projects: IFIGENIA (observational study in 10 Italian Local Health Units [LHUs]) on heterozygous familial hypercholesterolemia [HeFH]), CORE (database analysis on secondary prevention [SP] patients), HEALTH SEARCH (database analysis on patients at high and very high risk [HR/vHR] of cardiovascular events [CV]). RWD has been then discussed by a multidisciplinary panel and organized as evidences (RWE). RESULTS: According to IFIGENIA interim results on 3 LHUs, 0,20% of the patients with a LDL-C determination were probable or definite HeFH . Of those, 49% were treated with statins while 16% were treated with statin plus ezetimibe. Approximately half (46%) of HeFH patients were not adherent to statin and nearly all patients(98%) had not reached their LDL-C target according to the Italian Guidelines (NOTA 13). CORE estimated that 40% of patients were not treated with statin and/or ezetimibe within the first year of follow up. One-third (37%) of these SP patients is aged above 80, 38% experienced a new CV hospitalization within 12 months from the first CV event. HEALTH SEARCH highlighted that 69% of HR and 84% of vHR treated patients were not able to reach their LDL-C target. One-half of not at target vHR patients had a LDL-C >100 mg/dL. CONCLUSIONS: RWD is key to decrease the uncertainties within the healthcare decisions. These projects have demonstrated that there is a specific unmet need to be covered by PCSK9 inhibitors. Epidemiological and C-LDL data were key to size the impact of their introduction within the Italian National Healthcare System.