The purpose of this study was to evaluate if the variations of heart magnetic resonance imaging in beta-thalassemia major patients treated with Deferoxamine B mesylate (DF) or Deferiprone (L1) chelation therapy is a useful tool of the indirect myocardial iron content determination. For this reason, a prospective study was carried out. Seventy-two consecutive patients with beta-thalassemia major (35 treated with DF and 37 with L1) were studied. The main outcome results were laboratory parameters including determination of the liver iron concentration (LIC) and magnetic resonance imaging (MRI) of the heart and liver. The heart to muscle signal intensity ratios (HSIRs) were significantly increased in both the DF (t = -2.8; p < 0.01) and L1 (t = -3.1; p < 0.01) groups after one year of treatment No statistically significant difference in the values of HSIRs was present between the two groups at the beginning of treatment (p = 0.25; t = 1.13), and after one year of treatment (p = 0.20; t = 1.28). The HSIR were inversely correlated to the LIC (r = -0.52; p < 0.001) but not with ferritin levels (r = 0.10; p = 0.18). A positive correlation was found between the variation of HSIRs and that of the liver signal intensity ratios (r=0.52; p < 0.001), and a mild correlation (r = 0.40; p < 0.001) was found between the gamma glutamyltransferase (gammaGt) levels and the HSIRs values. Our data confirm that heart MRI is sensitive enough to detect significant variations of the mean HSIR during iron chelation with DF or L1.