The objective of this study was to investigate the prognostic significance of 12-lead electrocardiogram (ECG) patterns in a large multicenter cohort of patients with hypertrophic cardiomyopathy; 1,004 consecutive patients with hypertrophic cardiomyopathy and a recorded standard ECG (64% men, mean age 50 ± 16years) were evaluated at 4 Italian centers. The study end points were sudden cardiac death (SCD) or surrogates, including appropriate implanted cardiac defibrillator discharge and resuscitated cardiac arrest and major cardiovascular events (including SCD or surrogates and death due to heart failure, cardioembolic stroke, or heart transplantation). Prevalence of baseline electrocardiographic characteristics was: normal ECG 4%, ST-segment depression 56%, pseudonecrosis waves 33%, "pseudo-ST-segment elevation myocardial infarction (STEMI)" pattern 17%, QRS duration ≥120 ms 17%, giant inverted T waves 6%, and low QRS voltages 3%. During a mean follow-up of 7.4 ± 6.8years, 77 patients experienced SCD or surrogates and 154 patients experienced major cardiovascular events. Independent predictors of SCD or surrogates were unexplained syncope (hazard ratio [HR] 2.5, 95% confidence interval [CI] 1.4 to 4.5, p= 0.003), left ventricular ejection fraction <50% (HR 3.5, 95% CI 1.9 to 6.7, p= 0.0001), nonsustained ventricular tachycardia (HR 1.7, 95% CI 1.1 to 2.6, p = 0.027), pseudo-STEMI pattern (HR 2.3, 95% CI 1.4 to 3.8, p = 0.001), QRS duration ≥120 ms (HR 1.8, 95% CI 1.1 to 3.0, p = 0.033), and low QRS voltages (HR 2.3, 95% CI 1.01 to 5.1, p = 0.048). Independent predictors of major cardiovascular events were age (HR 1.02, 95% CI 1.01 to 1.03, p= 0.0001), LV ejection fraction <50% (HR 3.73, 95% CI 2.39 to 5.83, p= 0.0001), pseudo-STEMI pattern (HR 1.66, 95% CI 1.13 to 2.45, p= 0.010), QRS duration ≥120 ms (HR 1.69, 95% CI 1.16 to 2.47, p= 0.007), and prolonged QTc interval (HR 1.68, 95% CI 1.21 to 2.34, p= 0.002). In conclusion, a detailed qualitative and quantitative electrocardiographic analyses provide independent predictors of prognosis that could be integrated with the available score systems to improve the power of the current model.