BACKGROUND: Patients suffering from major beta thalassemia need frequent blood transfusions and, if not treated well, would be at risk of heart dysfunction. This study was performed to determine the diagnostic value of electrocardiography versus echocardiography in measuring the left ventricular mass index in these patients. METHODS: Between July 2010 and June 2011, 82 asymptomatic patients over 10 years of age with major thalassemia (42 men with a mean age of 17.65 ± 3.39 years and 40 women with a mean age of 16.9 ± 3.38 years) were enrolled in this study. For all the patients, standard electrocardiography (to measure R in aVL and S in V3 and calculate left ventricular mass index by electrocardiography) and echocardiography (to measure interventricular septum diameter in diastole, left ventricular posterior wall diameter in diastole, and left ventricular diameter in diastole in order to calculate left ventricular mass index by echocardiography) were performed, at least one week after transfusion. The calculated left ventricular mass indices were thereafter compared between the two methods (electrocardiography and echocardiography). RESULTS: Sensitivity, specificity, positive predictive value, and negative predictive value in the two techniques in determining the left ventricular mass index were 67%, 25%, 89%, and 7% in the females, 65%, 33%, 92%, and 6% in the males, and 67%, 14%, 89%, and 3% in the total population, respectively. Furthermore, this study demonstrated that the average left ventricular mass index by echocardiography and electrocardiography was 104.86 ± 21.65 gr/m2 and 91.69 ± 12.03 gr/m2, respectively. Echocardiography was much more accurate than electrocardiography in determining the left ventricular mass index (p value = 0.0001). CONCLUSION: The findings of this study demonstrated that echocardiography was more accurate and more reliable than electrocardiography in determining the left ventricular mass index in major thalassemia patients.