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BackgroundThere is emerging evidence suggesting that vitamin D and fibrinogen play contrasting roles in ACS pathophysiology and their combined impact, expressed as the vitamin D/fibrinogen ratio, can be a potential biomarker for ACS severity.This study aimed to investigate the relationship between vitamin D, fibrinogen, and their ratio with ACS types, and assess their potential as risk stratification biomarkers.MethodsThis multicenter observational study was conducted in tertiary care hospitals in Afghanistan, Egypt, and Pakistan, including 300 ACS patients. Serum vitamin D and fibrinogen levels were measured using electrochemiluminescence immunoassay and the Clauss method, respectively. Statistical analyses included ANOVA, Kruskal-Wallis, post-hoc Games-Howell tests, Spearman’s correlation, Fisher’s Z-test, and multivariable logistic regression.ResultsVitamin D levels were significantly lower (p ConclusionThe contrasting effects of vitamin D and fibrinogen can prove useful biomarkers and modifiable risk factors for ACS. The superiority of the vitamin D/fibrinogen ratio over vitamin D only, however, needs further validation in larger studies.