Objective: Assess achievement of low-density lipoprotein cholesterol (LDL-C) targets in European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines. Design: Systematic literature review. Data Sources: Medline, EMBASE, Cumulated Index to Nursing and Allied Health Literature. Eligibility Criteria: Observational studies reporting LDL-C levels/target attainment, measured between 1 August 2006 to 31 August 2017, in European adults with established cardiovascular disease (CVD), diabetes with target organ damage, familial hypercholesterolaemia (FH) or 10-year risk of fatal CVD ≥ 5% (assessed by Systematic Coronary Risk Evaluation [SCORE]). Data Extraction and Synthesis: Two reviewers independently extracted relevant studies and assessed study quality using the Risk of Bias for Non-Randomised Studies–Interventions (ROBINS-I) tool. Primary outcome was the proportion of patients achieving LDL-C targets in the 2011/2016 ESC/EAS guidelines. Where available, patient characteristics were presented as means weighted by sample size. The proportions of patients achieving LDL-C targets in the 5 years before and after publication of the 2011 guidelines were compared using a chi-square test. Results: Across 81 eligible studies (303,534 patients), achievement of LDL-C < 1.8 mmol/L was poor among patients with established CVD (16%; range 9–56%) and at very high risk of CVD (SCORE ≥ 10% [18%; 14–25%]). In individuals with FH, SCORE 5–10%, or diabetes and target organ damage, LDL-C < 2.5 mmol/L was achieved by 15% (9–22%), 46% (21–55%) and 13% (6–34%), respectively. Comparing the 5 years before/after publication of the 2011 guidelines, target achievement increased significantly over time but remained suboptimal (LDL-C < 1.8, 22% versus 15%; LDL-C < 2.5, 68% versus 61%; both p < 0.001; established CVD group only). Conclusions: These data show suboptimal LDL-C control among European patients at high risk of CVD. Those at greatest overall risk (clinically established CVD or at least a 10% 10-year risk of fatal CVD) had the lowest achievement of 2011/2016 EAS/ESC LDL-C targets. With lower LDL-C targets advocated in 2019 ESC/EAS guidelines, this unmet need will increase. Protocol Registration: PROSPERO registration number; CRD77844