The diagnosis and management of acute coronary syndrome (ACS) have improved significantly over the past few decades; however, the recognition of myocardial ischemia still proves to be a dilemma for cardiologists. The aim of this study was to determine the role of hematological and coagulation parameters in the diagnosis and prognosis of patients with ACS. This prospective study recruited 250 patients with ACS and 250 healthy controls. The diagnostic role of hematological and coagulation parameters was assessed by comparing the patients with ACS with the control group. The relationships between these parameters and mortality were determined by dividing the patients into 2 groups: Group A (discharged) and Group B (patients who died within 30 days of follow-up). Multivariate Cox regression analysis was performed to calculate the hazard ratio (HR). The mean age of the patients was 55.14±10.71 years, and 65.2% of them were male. Prothrombin time (P<0.001), activated partial thromboplastin time (P<0.001), mean platelet volume (MPV) (P<0.001), white blood cell (WBC) count (P<0.001), and red blood cell distribution width (RDW) (P<0.001) were significantly higher in the case group than in the control group. WBC count (P<0.001), RDW (P<0.001), and MPV (P<0.001) were significantly higher in the controls than in the case group. The Cox regression model showed that RDW above 16.55% (HR=6.8), MPV greater than 11.25 fL (HR=2.6), and WBC higher than 10.55×10/μL (HR=6.3) were the independent predictors of mortality. : In addition to being the independent predictors of short-term mortality, RDW, WBC, and MPV when used together with the coagulation profile may aid in the diagnosis of ACS in patients presenting with chest pain.