Introduction: In patients with recent acute coronary syndrome (ACS), PCSK9 inhibitors (PCSK9i), alirocumab and evolocumab, intensively decrease LDL-C and determine reduction of ischemic events. Yet, scant data are available on the initiation of PCSK9i in ACS patients in real-world setting.Aim: AT-TARGET-IT is an Italian multicenter prospective phase 4 registry involving 23 centers, designed to assess efficacy, safety and adherence of PCSK9i, as well as clinician’s behavior on lipid lowering therapies (LLT) in patients at very high CV risk. Aim of the current analysis is to report efficacy and safety in patients suffering ACS who received early prescription of PCSK9i during hospital stay, according to national reimbursement rules.Methods: From March 2020 through May 2023, we enrolled patients receiving PCSK9i as part of their optimal medical therapy. Clinical, laboratory and demographic characteristics and concomitant therapies were recorded at the time of first prescription and in subsequent follow-up.Results: We report 405 patients (22% female, age 61 years, 60% chronic coronary syndromes). Median LDL-C was 142 mg/dL at hospital admission, reached 45 mg/dL at first control (time 37 days, 67% reduction, 97 mg/dl absolute reduction) and remained unchanged at latest lipid control (time 11 months, 66% reduction, 94 mg/dl absolute reduction). Of 405 patients enrolled, 252 patients (62%) were receiving LLT at time of hospital admission, of them 91 (36%) were on ezetimibe, 48 (19%) on statin and 113 (45%) were on a statin and ezetimibe combination. LDL-C target according to the ESC guidelines was reached in 272 patients (67%), with differences based on LLT (Figure 1-A). Also LDL-C percentage reduction was influenced by background LLT (Figure 1-B). No serious adverse reactions were reported.Conclusions: Early PCSK9i administration effectively reduces LDL-C in ACS patients in the real-world setting. However, concomitant LLT is needed to optimize early LDL.values.