PURPOSE: Coronary artery disease (CAD), clinically manifested as coronary syndrome (CS), is the leading cause of death and a significant contributor to morbidity worldwide. Elevated serum homocysteine levels have been associated with an increased risk of cardiovascular diseases, including CAD. Despite extensive research, the relationship between serum homocysteine and coronary syndromes with related short-term mortality is still under-studied. The main objective of this study is to evaluate the correlation between serum homocysteine levels and various types of CS, as well as in-hospital mortality in these patients. PATIENTS AND METHODS: This multicenter study included 381 CS patients from Afghanistan, Egypt, and Pakistan tertiary care hospitals. The relation of serum homocysteine levels with different types of CS as well as with in-hospital mortality was measured and analyzed using inferential statistics (ANOVA, Kruskal-Wallis test, Tukey's post-hoc, Pearson correlation, etc.) and regression analysis (Binary regression). RESULTS: Among 381 patients from both genders, 160 were from Pakistan, 130 from Egypt, and 91 from Afghanistan. There was no significant difference in baseline characteristics, like age, gender, homocysteine level, CS type, and mortality, among the three countries ( CONCLUSION: Serum homocysteine could serve as a valuable biomarker and mortality predictor in CS patients.