Background: Growth differentiation factor 15 (GDF15) gene expression level is a novel biomarker that reflects inflammation and oxidative stress in patients with acute coronary syndrome and those complicated with type 2 diabetes mellitus (T2DM). Growth differentiation factor 15 high levels could be a reliable sensitive biomarker for the prediction of acute coronary syndrome. Patients and Methods: This Cross-sectional/case-control study was conducted at the Cardiology Department, Assiut University during the period from January 2018 to December 2019, and patients were selected with the exclusion of any inflammatory or autoimmune disease. Results: Growth differentiation factor 15 gene expression was significantly higher in acute coronary syndrome patients compared to the controls (p-value <0.001) and its expression was significantly higher in acute coronary syndrome patients with type 2 diabetes mellitus group compared to acute coronary syndrome patient group (p-value<0.05). Growth differentiation factor 15 had 92% sensitivity and 77% specificity in the prediction of acute coronary syndrome which was statistically significant (p-value< 0.001), while yielded 73% sensitivity and 53% specificity of no statistical significance (p-value=0.829) in the prediction of type 2 diabetes mellitus among patients with acute coronary syndrome. Conclusion: Growth differentiation factor 15 gene expression could be used as a reliable sensitive biomarker for prediction of the acute coronary syndrome but more studies will be mandatory soon to clarify its role as a predictive marker for type 2 diabetes mellitus development among patients with the acute coronary syndrome.