Introduction: The aim of this study was to determine the risk assessment of acute coronary syndrome and prediction of major adverse cardiac events by HEART (History, ECG, Age, Risk factors, Troponin) and HEARTS3 (HEART + 3S = Sex, Serial 2-h ECG, and Serial 2-h delta Troponin) scoring systems in patients admitted to the emergency department with chest pain. Methods: This is a single-center prospective cohort study. This study was conducted in patients admitted to the emergency department with chest pain, without ST-elevation myocardial infarction, who were 18 years or older, and agreed to participate in the study. The primary endpoint is the occurrence of major adverse cardiovascular events within 30 days. The receiver operating characteristic curve was used to assess the power of HEART and HEARTS3 scores to predict major adverse cardiovascular events. Results: The mean age of 239 patients was 47.91 ± 13.93 years and 72.4% (173) were male. Major adverse cardiovascular events developed in 20.1% (48) of the patients. The mean HEART and HEARTS3 scores of the patients with major adverse cardiovascular events (5.67 ± 1.46 and 9.38 ± 3.91, respectively) were both statistically and significantly higher than the scores of the patients without major adverse cardiovascular events (2.33 ± 1.44 and 2.22 ± 1.39; p = 0.001). The area under the curve values of HEART and HEARTS3 scores were found to be 0.943 (95% confidence interval: 0.905–0.968) and 0.990 (0.968–0.999), respectively. Conclusion: In our study, the power of HEARTS3 score to predict major adverse cardiovascular events was better in the risk assessment of acute coronary syndrome in patients admitted to the emergency department with chest pain compared to the HEART score. We think that patients with a low HEARTS3 score can be safely discharged from emergency department without further cardiac examination.