Aims: To assess whether implementation of the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) dyslipidaemia guidelines observed between 2020 and 2021 improved between 2021 and 2022 in the SANTORINI study., Methods and Results: Patients with high or very high cardiovascular (CV) risk were recruited across 14 European countries from March 2020 to February 2021, with 1-year prospective follow-up until May 2022. Lipid-lowering therapy (LLT) and 2019 ESC/EAS risk-based low-density lipoprotein (LDL) cholesterol (LDL-C) goal attainment (defined as <1.4 mmol/L for patients at very high CV risk and <1.8 mmol/L for patients at high CV risk) at 1-year follow-up were compared with baseline. Of 9559 patients enrolled, 9136 (2626 high risk and 6504 very high risk) had any available follow-up data, and 7210 (2033 high risk and 5173 very high risk) had baseline and follow-up LDL-C data. Lipid-lowering therapy was escalated in one-third of patients and unchanged in two-thirds. Monotherapy and combination therapy usage rose from 53.6 and 25.6% to 57.1 and 37.9%, respectively. Mean LDL-C levels decreased from 2.4 to 2.0 mmol/L. Goal attainment improved from 21.2 to 30.9%, largely driven by LLT use among those not on LLT at baseline. Goal attainment was greater with combination therapy compared with monotherapy at follow-up (39.4 vs. 25.5%)., Conclusion: Lipid-lowering therapy use and achievement of risk-based lipid goals increased over 1-year follow-up particularly when combination LLT was used. Nonetheless, most patients remained above goal; hence, strategies are needed to improve the implementation of combination LLT., Competing Interests: Conflict of interest: K.K.R. has received honoraria for consulting, lectures from Abbott Laboratories, Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim, Cargene, CRISPR, Daiichi Sankyo, Eli Lilly Company, Emendobio, Esperion, Kowa, New Amsterdam Pharma, Novartis Corporation, Nodthera, GSK, Novo Nordisk, Pfizer, Regeneron, Sanofi, SCRIBE, Silence Therapeutics, and VAXXINITY. In addition, he has received research grant support to his institution from Amgen, Daiichi Sankyo, Sanofi, Regeneron, and Ultragenyx, plus stock options from New Amsterdam Pharma, Scribe, and Pemi 31. A.L.C. received research grant support from Amryt Pharma, Menarini, Ultragenyx, and Viatris, and lecturing fees from Amarin, Amgen, Amryt Pharma, AstraZeneca, Daiichi Sankyo, Esperion, Ionis Pharmaceutical, Medscaper, Menarini, Merck, Novartis, Peervoice, Pfizer, Recordati, Regeneron, Sandoz, Sanofi, The Corpus, Ultragenyx, and Viatris. M.A. received research grant support and lecturing fees from Alfasigma, Amgen, Amryt, Daiichi Sankyo, Ionis Pharmaceuticals/Akcea Therapeutics, Novartis, Pfizer, Regeneron Pharmaceuticals, Sanofi, Sobi, Viatris, and Ultragenyx. A.B., R.C., M.L., and J.S. are employees of Daiichi Sankyo. H.T. received grant support and lecturing fees from Daiichi Sankyo and participated in an advisory board run by Daiichi Sankyo. T.S. received consulting fees from Amgen, Novartis, Orion Pharma, and Valio, and lecturing fees from Amarin, Pfizer, and GSK. He is a patient on statin and ezetimibe therapy. U.L. received grant support from Daiichi Sankyo, Novartis, and Amgen and lecturing fees from Daiichi Sankyo, Novartis, Amgen, Sanofi, Boehringer, MSD, Pfizer, Lilly, and AstraZeneca. He has also been a member of advisory boards for Daiichi Sankyo, Novartis, Amgen, Sanofi, Boehringer, and MSD, in addition to donning leadership/fiduciary roles with EAS, ESC, DGK, and DACH., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)