BACKGROUND & AIMS: We investigated whether tissue elastography (TE) can be used as an alternative to magnetic resonance imaging (MRI) T2* analysis to determine the degree of iron overload in patients with thalassemia major. METHODS: We conducted a prospective study of 154 patients (99 male; mean age, 12 +/- 3.6 years) with thalassemia major requiring chronic blood transfusion and on iron chelator therapy. The study was performed at a tertiary hospital in India from January 2015 through June 2015. We performed routine blood sample analyses, measurements of serum levels of ferritin, and TE within 1 month of MRI T2* analysis of the liver. The Spearman correlation test and linear regression analysis were used to evaluate the correlation between TE liver stiffness measurements and R2* MRI results or serum ferritin levels. RESULTS: The subjects' mean total serum levels of bilirubin, alanine aminotransferase, aspartate aminotransferase, and albumin were 1.4 +/- 0.6 mg/ dL, 65.0 +/- 51.8 IU/L, 62.9 +/- 44 IU/L, and 4.2 +/- 0.2 g/ d, respectively. Mean liver stiffness measurement, MRI T2* (3 T), corresponding MRI R2* ( 3 T), and ferritin values were 8.2 +/- 4.4 kPa, 3.18 +/- 2.6 milliseconds, 617.3 +/- 549 Hz, and 4712 +/- 3301 ng/mL, respectively. On the basis of MRI analysis, 67 patients (43.5%) had mild iron overload, 49 patients (31.8%) had moderate iron overload, and 22 patients (14.3%) had severe iron overload. Fibroscan liver stiffness measurements correlated with MRI R2* values (r = 0.85; P < .001). TE results identified the patients with severe, moderate, and mild iron overload with area under the receiver operating characteristic curve values of 94.8%, 84.5%, and 84.7%, respectively. Liver stiffness measurements greater than 13.5, 7.8, and 5.5 kPa identified patients with severe, moderate, and mild iron overload, respectively; the sensitivity and specificity values were 92% and 93% for severe overload, 82% and 82% for moderate overload, and 73% and 75% for mild overload. No correlation was found between TE results and serum level of ferritin (r = 0.19; P = .11). CONCLUSIONS: Results of TE correlate with those from MRI T2* analysis. TE is cheaper and more available than MRI and might be used to estimate hepatic iron overload, especially moderate to severe overload in patients with thalassemia major who require chronic transfusion.