Objectives The objective of this study was to examine the association between exercise capacity and echocardiographic indexes of atrial and ventricular function and size in patients with β-thalassemia major. Background In patients with β-thalassemia major, the assessment of cardiac function with echocardiography alone does not always correspond to their functional status. Peak oxygen uptake and anaerobic threshold, on the other hand, constitute 2 objective and reproducible determinants of exercise capacity in patients with heart failure. Methods and Results Forty consecutive patients (22 women and 18 men, 18 to 30 years old) who were in stable condition while receiving regular transfusions and 30 age- and sex-matched control subjects were studied. At 2 to 3 days after the last transfusion, each subject underwent complete echocardiographic study followed by cardiopulmonary exercise testing. Left atrial volumes (maximal [Vmax], at onset of atrial systolic [Vp], and minimal [Vmin]) and left ventricular volumes were measured with the biplane area-length method, and left atrial active emptying fraction (ACTEF) and left ventricular ejection (LVEF) fraction were calculated. Peak oxygen uptake (V̇o₂ max) and anaerobic threshold (AT) were also estimated. After transfusion, patients with β-thalassemia major had reduced V̇o₂ max and AT and greater left atrial volume in comparison with control subjects. Also, ACTEF and LVEF were significantly lower in the patient group. Moreover, V̇o₂ max and AT were inversely related to Vmax (r = –0.74 and r = –0.80, respectively) and directly related to ACTEF (r = 0.85 and r = 0.82, respectively) in β-thalassemia major, whereas they were poorly related to LVEF (r = 0.50 and r = 0.53, respectively). In the control group, V̇o₂ max and AT parameters were related to Vmax and ACTEF in a similar way to that in the β-thalassemia group. Conclusions In patients with β-thalassemia major, exercise capacity does not correlate with left ventricular dimensions and function. On the contrary, left atrial size and systolic dysfunction are probably predictors of decreased exercise capacity. (Am Heart J 1998;136:988-90.)