Background: Current European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines for the management of dyslipidemias have further reduced low density lipoprotein-cholesterol (LDL-C) targets, as compared to the guidelines released in 2016. These targets are particularly restraining for patients at very high risk (VHR). Methods: Using the data from a nationwide, prospective registry on patients with established atherosclerotic cardiovascular disease (ASCVD), we sought to assess: 1) the contemporary use of conventional cholesterol-lowering therapies and the achievement of LDL-C goals according to previous and current ESC guidelines in subjects at VHR; 2) the proportion of VHR patients potentially eligible for proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) treatment. Results: Among the 5053 patients with data available, 4751 (94.0%) were deemed as VHR. Among these patients, the mean LDL-C levels were 62.4 ± 47.7 mg/dl at enrollment. A high dose of statin was used in 54.9%, while the association of high dose statin and ezetimibe was prescribed in 4.8% of VHR patients. A target level of LDL-C < 70 mg/dl recommended by 2016 ESC guidelines was reached by 58.1%, while a target of <55 mg/dl and LDL-C reduction ≥50% recommended by 2019 ESC guidelines, would be reached by 3.2% of patients at VHR. Accordingly, 9.4% and 1.4% of VHR patients would be eligible for PCSK9i according to ESC guidelines and Italian regulations, respectively. Conclusions: In VHR patients enrolled in this large cohort of established ASCVD managed by cardiologists, the lipid management and LDL-C targets attainment is largely suboptimal. © 2020 Elsevier B.V.