BACKGROUND: Cardiovascular disease is one of the leading causes of death worldwide. According to the results of various studies, protein convertase subtilisin kexin type-9 (PCSK9) was determined as a novel risk factor for stable coronary artery disease. Few studies have investigated the relationship between PCSK9 levels and the severity of coronary artery disease in patients with acute coronary syndrome; thus, we herein aimed to investigate this relationship in patients with non-ST-elevation myocardial infarction (NSTEMI) who underwent coronary angiography. PATIENTS AND METHODS: Herein, 168 patients with NSTEMI were prospectively enrolled, and severity of atherosclerotic lesions was determined using SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery (SYNTAX), Gensini and Jeopardy scores. Plasma PCSK9 levels, lipid parameters and C-reactive protein levels were measured after a 12-h fasting period. The relationship of PCSK9 levels and clinical and laboratory parameters of patients with their SYNTAX, Gensini and Jeopardy scores was investigated. RESULTS: Pearson correlation analysis showed a strong positive correlation between PCSK9 and the three scores (P < 0.001, r > 0.5 for all). In ROC analysis, a mid-high SYNTAX score of at least 25 was predicted with a sensitivity of 81% and a specificity of 63% when the PCSK9 level was higher than 52.8 ng/ml (area under a curve 0.76, P < 0.001). Multivariate linear regression analysis revealed that PCSK9, low-density lipoprotein cholesterol and creatinine levels were independent predictors of a high SYNTAX score. CONCLUSION: Taken together, high PCSK9 levels may be a risk factor for adverse events in patients with NSTEMI. Aggressive lipid-lowering therapies may benefit this group of patients.