Ventricular tachycardia (VT) resulting from arrhythmogenic right ventricular cardiomyopathy (ARVC) may be difficult to differentiate from idiopathic right ventricular outflow tract (RVOT) VT. The purpose of this study was to investigate the hypothesis that QRS characteristics would be different in ARVC because of altered conduction through abnormal myocardium. In 24 RVOT VT patients (18 women and 6 men; age 42 ± 10 years) and 20 ARVC patients (12 women and 8 men; age 38 ± 14 years), mean QRS duration, frontal plane axis, and precordial R-wave transition were measured in 12-lead ECGs recorded during VT. Mean QRS duration was longer in all 12 leads in ARVC patients. A significant difference was noted in leads I, III, aVL, aVF, V 1 , V 2 , and V 3 (P <.05). Leads I and aVL had the largest mean difference between ARVC and RVOT VT patients of 17.6 ± 4.7 ms and 15.8 ± 7.5 ms, respectively (P <.0001). Lead I QRS duration ≥120 ms had a sensitivity of 100%, specificity 46%, positive predictive value 61%, and negative predictive value 100% for ARVC. The area under the receiver operating characteristic (ROC) curve was 0.89. The addition of mean QRS axis <30° (R<S in lead III) to the above criterion increased specificity for ARVC to 100%. QRS duration remained sensitive and specific in the subgroup of nine ARVC ECGs with an inferior axis (ROC area 0.82). R-wave transition was not different between groups. QRS duration is longer in ARVC compared with RVOT VT. An algorithm combining lead I QRS duration for sensitivity and axis for specificity is useful for differentiating the two tachycardia substrates.