Background: We aimed to investigate the association of serum cathepsin D levels with in-hospital mortality and Syntax scores (SXscore) in non-ST elevation myocardial infarction (NSTEMI) patients. Methods: A total of 88 patients were included in the study. The patients were divided into two groups: those with in-hospital mortality (-), and those with in-hospital mortality (+). The receiver operating characteristics curve was used to showthe sensitivity and specificity of serum cathepsin D levels, and the optimal cut-off value for predicting in-hospital mortality and high SXscore. Results: Patients with (+) in-hospital mortality and high SXscore had lower serum cathepsin D levels compared to the patients with (-) in-hospital mortality and low SXscore. Using a cutoff score of < 16 for the cathepsin D level, in-hospital mortality was predicted with a sensitivity and specificity of 73.4% and 77.6%, respectively, and also predicted high SXscore with a sensitivity and specificity of 72.4% and 67.6%, respectively. Conclusions: Serum cathepsin D levels established upon admission were significantly and independently lower in NSTEMI patients with high rate of mortality, high SXscores, and low left ventricular ejection fraction.