Accurate assessment of liver iron concentration (LIC) is critical for optimal monitoring of iron toxicity in multitransfused patients. Serum ferritin is the most widely used although its association to LIC is only modest. We studied if a liver-specific measure using dual-energy X-ray absorptiometry (DXA) systems could improve LIC estimates over ferritin alone in Thalassemia (Thal) patients. Thirty-seven patients with Thal (19.2 ± 9.0 yr, 20 male) were studied and 10 had multiple visits. Height, weight, ferritin, whole-body DXA, and hepatic superconducting quantum interference device (SQUID) were measured within 5 wk. DXA hepatic density was measured using right rib, whole liver, and multiple subliver regions. The best agreement to SQUID LIC was found using a combination of ferritin, weight, DXA subliver region 3 bone mineral content (BMC), and right rib BMC. DXA with ferritin improved the ferritin alone correlation from R(2)=0.35 to R(2)=0.62. Serial LIC changes using DXA were associated with serial SQUID changes (r=0.73, p=0.02). Changes in ferritin alone were not significant (p=0.06). We conclude that the addition of whole-body DXA measures and body weight substantially increased the accuracy of LIC and change in LIC estimates over the use of ferritin alone and could be useful when magnetic resonance imaging or SQUID is not available.