Aim This study evaluated the prognostic ability of the APACHE II score and compared it with inflammatory indices in patients with acute coronary syndrome (ACS).Material and Methods A total of 525 patients with ACS were retrospectively enrolled in the study. APACHE II scores were calculated and C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), and systemic immune-inflammatory index (SII) were recorded. The APACHE II score was compared with inflammatory indices for predicting in-hospital mortality.Results Univariate logistic regression (LR) analysis showed that CRP, SII, NLR, ejection fraction, chronic kidney disease, gender, and APACHE II score were significant predictors of mortality. In multiple LR analysis, the APACHE II score was found to be a solitary, significant predictor of in-hospital mortality (OR: 1.201, 95 % CI: 1.122-1.285; p<0.001). In the Receiver Operating Characteristics curve, using a cut-off point of 16.5, the APACHE II score predicted in-hospital mortality with 70.4 % sensitivity and 92.9 % specificity.Conclusion The APACHE II score may be used as a predictor of in-hospital mortality better than inflammatory markers in ACS patients.