Tissue Doppler imaging (TDI) can detect myocardial dysfunction related to iron load in patients with beta-thalassemia major (TM). We aimed to assess the efficacy of pulsed-wave TDI (PW-TDI) in predicting myocardial iron load in patients with TM using T2* magnetic resonance (MR) as the gold-standard non-invasive diagnostic test. 33 asymptomatic TM patients, mean aged 18 ± 6 years (6–31) with normal left ventricular (LV) global systolic function were evaluated by conventional echocardiography and PW-TDI. Results were compared with 20 age and sex-matched controls. TDI measures included myocardial systolic (Sm), early (Em) and late (Am) diastolic velocities at basal and middle segments of septal and lateral LV wall. Myocardial iron deposition were measured in 29/33 patients by T2* MR. TM patients were also subgrouped according to those with iron load (T2* ≤ 20 ms) and those without (T2* > 20 ms). Mean T2* was 12.3 ± 7.8 ms (4–31.3). Abnormal myocardial iron load (T2* < 20 ms) was found in 25/29 (86%) patients. The following TDI measures were lower in patients than in controls: basal septal Em (P < 0.001) and Am (P < 0.05), mid-septal Am (P < 0.05), mid-lateral LV wall Sm (P < 0.05) and Am (P < 0.05). Regional myocardial dysfunction were more prominent in patients with T2* ≤ 20 ms. Mid-septal Sm and Em significantly correlated with mid-septal T2*(r = 0.44, P = 0.023 and r = 0.54, P = 0.004, respectively). The PW-TDI parameters and the cut-off values for predicting presence of myocardial iron load were determined. PW-TDI technique was found both sensitive and specific in predicting presence of myocardial iron load in TM patients with normal LV global systolic function. Therefore, it can be used for screening of TM patients.