Background: Doppler echocardiographic studies of the left ventricle (LV) function in patients with beta-Thalassemia Major (beta-TM) had shown different patterns of systolic and diastolic dysfunctions associated with abnormal serum brain natriuretic peptide (BNP). Aim: This cross-sectional study was designed to study the LV systolic and diastolic functions and correlate that with serum level of N-terminal pro brain natriuretic hormone (NT-pro BNP) in patients with beta-TM using Pulsed Doppler (PD) and Tissue Doppler (TD) echocardiography. Methods: The study was conducted on patients with beta-TM (n = 38, age 15.7 +/- 8.9 years) and compared with an age-matched controls (n = 38, age 15.9 +/- 8.9 years). In all participants, PD and TD echocardiography were performed and blood samples were withdrawn for measuring the serum level of NT-pro BNP, ferritin, and alanine transaminase. Results: Patients with beta-TM compared with controls, have thicker LV septal wall index (0.65 +/- 0.26 vs. 0.44 +/- 0.21 cm, P < 0.001), posterior wall index (0.65 +/- 0.23 vs. 0.43 +/- 0.21 cm, P < 0.01), and larger LVEDD index (4.35 +/- 0.69 vs. 3.88 +/- 0.153 mm, P < 0.001). In addition, beta-TM patients have higher transmitral E wave velocity (E) (70.818 +/- 10.139 vs. 57.532 +/- 10.139, p = 0.027) and E/A ratio (1.54 +/- 0.17 vs. 1.23 +/- 0.19, P, 0.01) and shorter deceleration time (DT) (160.13 +/- 13.3 vs. 170.50 +/- 19.20 m sec, P, 0.01). Furthermore, the ratio of transmitral E wave velocity to the tissue Doppler E wave at the basal septal mitral annulus (E/Em) was significantly higher in beta-TM group (19.6 +/- 2.81 vs. 13.868 +/- 1.41, P < 0.05). The tissue doppler systolic wave (Sm) velocity and the early diastolic wave (Em) were significantly lower in beta-TM group compared to controls (Sm: 4.82 +/- 1.2 vs. 6.22 +/- 2.1 mm/sec, P < 0.05; Em: 3.51 +/- 2.7 vs. 4.12 +/- 2.5 mm/sec P < 0.05, respectively). The tricuspid valve velocity was significantly higher in beta-TM patients compared with controls (2.993 +/- 0.569 vs. 1.93 +/- 0.471 m/sec, respectively, P < 0.01). The mean serum NT pro-BNP in beta-TM was significantly higher compared with controls (37.6 +/- 14.73 vs. 5.5 +/- 5.4pg/ml, P, 0.05). The left ventricle ejection fraction (EF%) and fractional shortening (FS%) were not significantly different between both groups. Conclusion: We conclude that patients with beta-TM had a significantly higher serum level of NT-pro BNP that is positively correlated with the E/Em ratio on tissue Doppler. Furthermore, we confirm our previous findings that patients with beta-TM exhibit LV diastolic -pattern on echocardiogram suggestive of restrictive type with well preserved left ventricle systolic function.