Background More than 70% of thalassemia’s major mortality is due to the cardiac complications of this syndrome, mostly consequent to myocardial Iron overload; therefore, evaluation of such complications is of utmost importance. T2*MRI is used to assess hepatic and myocardial Iron load in thalassemia patients, which is not always available. Signal-Averaged Electrocardiography is a rather easy method of evaluating major thalassemia patients regarding their risk for sudden cardiac death. Methods and materials In this cross-sectional study, 48 patients with thalassemia major underwent evaluation with electrocardiography, signal-averaged electrocardiography, echocardiography, T2*MRI, and ferritin level. The association of the existence of ventricular late potentials in SAECG and other cardiac variables was evaluated. Moreover, the association between myocardial and hepatic Iron load and cardiac characteristics was assessed. Results 48 patients with a mean age of 30.31 ± 7.22 years old entered the study. 27 (56.3%) of the patients had ventricular late potentials, which were associated with myocardial dry Iron weight (P = 0.011). Nonspecific ST-T changes and premature atrial and ventricular contractions were seen more frequently in patients with late potentials (P = 0.002, 0.031, and 0.031, respectively). Patients with higher myocardial and hepatic Iron loads had longer QTc in their 12-lead surface electrocardiograms. Conclusion Patients with ventricular late potentials assessed by SAECG had a higher myocardial Iron load. Higher myocardial Iron load is associated with higher cardiac complications in patients with beta-thalassemia major; therefore, SAECG can be used as a screening test for cardiac complications in beta-thalassemia major patients.