Background: Red blood cell (RBC) transfusion is the treatment basis in beta-thalassemia major. Aim: With the present study we aimed to investigate the effect of RBC transfusions on tissue oxygenation, in beta-thalassemics. Microcirculatory indices obtained by Near Infrared Spectroscopy (NIRS) were utilized. Methods: The relative oxyhemoglobin concentration in tissues (StO2), as assessed by NIRS, was measured before and 30 min after a regular transfusion, in 17 consecutive beta-thalassemia major patients. The NIRS probe was placed on the thenar eminence. The oxygen consumption rate (%/min) during a 3 min vascular occlusion and the reperfusion rate after occlusion release were also estimated. Results: The patients received 7.85±1.98 ml/kg packed leukocyte-depleted RBC. StO2 increased significantly after RBC transfusion compared to baseline (90% vs. 88% respectively, p=0.002). Delta StO2 (StO2 change after RBC transfusion) showed a significant negative correlation with baseline StO2. The O2 consumption rate after occlusion showed no significant change after RBC transfusion, while the reperfusion rate displayed an increasing trend of borderline significance (p=0.076). Conclusion: The present study indicates that regular RBC transfusions improve microcirculation in beta-thalassemia major patients.