Iron chelation therapy in patients with thalassemia major may not prevent iron overload in all organs, especially those in which iron enters cells through specific calcium channels. We designed a controlled pilot study to assess the potential of the calcium channel blocker amlodipine in strengthening the efficacy of iron chelation. Fifteen patients with thalassemia major undergoing chelation therapy were randomized to receive amlodipine added to standard treatment in a 1:2 allocation for 12 months. T2* values for assessment of iron overload in the liver and heart using magnetic resonance imaging were obtained at baseline and at 6 and 12 months. In the amlodipine-treated group, heart T2* increased significantly in comparison to baseline at 6 and 12 months (21.7 ± 7.2 ms to 28.2 ± 7.9 ms and 28.3 ± 8.0 ms, with P = .007 and .03, respectively), while no differences were observed in the control group (25.1 ± 8.8 ms to 24.7 ± 7.8 ms and 26.2 ± 11.4 ms; P = .99 and 0.95, respectively); significant differences between groups were observed at 6 months (28.2 ± 7.9 ms vs 24.7 ± 7.8 ms in the control group, P = .03). A significant reduction in ferritin levels also was observed in the treated group at 12 months. The use of amlodipine in conjunction with standard chelation therapy may suggest a new strategy in preventing and treating iron overload in patients with thalassemia major, especially in organs where iron absorption depends on active uptake by calcium channels like the heart.126834-7