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The GRACE score constitutes a useful tool for risk stratification in patients with acute coronary syndrome (ACS), while the SYNTAX score determines the complexity of coronary artery disease (CAD). This study sought to correlate these scores and assess the accuracy of the GRACE score in predicting the extent of CAD. A total of 539 patients with ACS undergoing coronary angiography were included in this analysis. The patients were classified into those with a SYNTAX score &lt, 33 and a SYNTAX score ≥ 33. Spearman’s correlation and receiver operator characteristic analysis were conducted to investigate the role of the GRACE score as a predictor of the SYNTAX score. There was a significantly positive correlation between the SYNTAX and the GRACE scores (r = 0.32, p &lt, 0.001). The GRACE score predicted severe CAD (SYNTAX ≥ 33) moderately well (the area under the curve was 0.595 (0.522–0.667)). A GRACE score of 126 was documented as the optimal cut-off for the prediction of a SYNTAX score ≥ 33 (sensitivity = 53.5% and specificity = 66%). Therefore, our study reports a significantly positive correlation between the GRACE and the SYNTAX score in patients with ACS. Notably, NSTEMI patients with a high-risk coronary anatomy have higher calculated GRACE scores. A multidisciplinary approach by a heart team could possibly alter the therapeutic approach and management in patients presenting with ACS and a high calculated GRACE score.