Many patients with sickle cell disease receive blood transfusions as a life-saving treatment. However, excess transfusions may lead to increased body iron burden. Specifically, heart failure due to cardiac iron overload is the leading cause of death in these patients. The purpose of this study was to investigate the potential role of high-field 3.0-Tesla (T) cardiovascular magnetic resonance (CMR) for assessment of cardiac iron content by measuring the transverse relaxivity rate R2*. The R2* was measured in calibrated phantoms with different iron concentrations at 3.0T and 1.5T using optimized pulse sequences. Myocardial R2* was measured at 3.0T in a group of sickle cell disease patients with different disease stages, and the results were compared to the serum ferritin levels and hepatic R2*. The phantom R2* measurements at 3.0T were double those at 1.5T, and the measurements of both systems showed linear relationships with iron concentration. The 3.0T R2* was more sensitive than 1.5T in detecting low iron concentration. In patients, myocardial R2* had weak and good correlations with hepatic R2* and serum ferritin levels, respectively. Bland-Altman analysis showed low inter- and intra-observer variabilities. In conclusion, measuring myocardial R2* at 3.0T is a promising technique with high sensitivity and reproducibility for evaluating cardiac iron overload in sickle cell disease patients.