Background: Global Registry of Acute Coronary Events (GRACE) score has been routinely used for risk stratification in acute coronary syndromes (ACS). We aimed to investigate whether the GRACE score has remained relevant with contemporary treatment of patients with ACS. Methods: Included were patients with ACS in the Acute Coronary Syndrome Israeli Survey (ACSIS). Patients were divided into high (> 140) and low–intermediate (≤ 140) GRACE score. Outcomes were compared for each GRACE score group among patients enrolled in early (2000 to 2006), mid (2008 to 2010) and late (2013 to 2016) surveys. Results: Included were 4931 patients. For patients with GRACE scores > 140, temporal improvements in therapy were associated with reduced 7-day all-cause mortality (5.7%, 4.1%, and 2.0% for patients in early, mid-, and late surveys, respectively, P = 0.01) and 1-year mortality rates (27.8%, 25.3%, and 21.8% for patients in early, mid-, and late surveys, respectively, P = 0.07). Among patients with GRACE scores ≤ 140, all-cause mortality rates at 1 year were lower among participants enrolled in recent surveys (5.3%, 3.5%, and 3.1% for patients in early, mid-, and late surveys, respectively, P = 0.01). No significant differences in the accuracy of the GRACE score in predicting 7-day mortality were observed, (area under the curve [AUC] = 0.83, 0.87, and 0.75 for early, mid-, and late surveys, respectively, P = NS). Similarly, for 1-year all-cause mortality, the accuracy of the GRACE score remained comparable (AUC = 0.79, 0.84, and 0.82 for early, mid-, and late surveys, respectively, P = NS). Conclusions: Our results validated the accuracy of the GRACE score for risk stratification in ACS. The discrimination of the score has not been influenced by the better outcome with latest treatment.