In the prospective, multinational Global Registry of Acute Coronary Events (GRACE), patients diagnosed with non-ST-elevation acute coronary syndromes had their admission electrocardiogram independently evaluated by a central core laboratory, and its interpretation by the core laboratory and enrolling site were compared. One in 6 of these patients had clinically important features of left-bundle branch block or ST-segment deviation diagnosed by the core laboratory that were apparently not recognized at the local sites; this subgroup of patients was less likely to undergo risk stratification and revascularization. Importantly, failure to recognize these features as confirmed by the core laboratory in routine clinical practice was independently associated with higher mortality and recurrent myocardial infarction at 6 months (adjusted odds ratio 1.41, 95% confidence interval 1.01 to 1.96, p = 0.043). In conclusion, these findings underscore an urgent need to promote more accurate interpretation of electrocardiograms in contemporary clinical practice to bridge treatment gaps and improve patient outcome.