Background: For cardiologists, management of acute chest pain continues to be a challenge. Physicians struggle to avoid unnecessary admissions and at the same time not to miss highrisk patients needing urgent intervention. Therefore, diagnostic strategies focus on identifying patients in whom an acute coronary syndrome can be safely ruled out based on findings from history, physical examination, and early cardiac marker measurement. The HEART score, a clinical prediction rule, was developed to provide the clinician with a simple and reliable predictor of cardiac risk. Aim: This study aimed to investigate the role of neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) as independent laboratory biomarkers when associated with the HEART risk score. Method: A cross-sectional study of 120 patients who attended the emergency department with acute chest pain. NLR and PLR were both measured. In addition, the HEART score was the valid instrument used in evaluating and risk stratifying patients into low-, intermediate-, and high-risk group. Results: There was a positive correlation between the HEART score and the mean PLR and NLR (p = 0.000*). PLR and NLR were found to be significantly higher in the high-risk HEART score group (p = 0.05 and 0.0001*, respectively). A PLR of 115.5 and above had a sensitivity of 73% and specificity of 78%, while an NLR of 3.95 and above had a sensitivity of 75% and specificity of 86% to detect high-risk HEART score patients. Conclusion: PLR and NLR proved to be a useful tool to identify highrisk patients when validated against the HEART score.