Abstract Background The leading cause of mortality of thalassemia major patients is iron overload cardiomyopathy. Early diagnosis with searching for left ventricular diastolic dysfunction before the systolic dysfunction ensued might yield better prognosis. This study aimed to define the prevalence of the left ventricular diastolic dysfunction (LVDD) in thalassemia major patients with normal left ventricular systolic function and the associated factors. Methods Adult thalassemia major patients with normal left ventricular systolic function who were referred for cardiac T2* at Siriraj Hospital – Thailand’s largest national tertiary referral center – during the October 2014 to January 2017 study period. Left ventricular diastolic function was defined by mitral valve filling parameters and left atrial volume index using CMR. Patients with moderate to severe valvular heart disease, pericardial disease, or incomplete data were excluded. Baseline characteristics, comorbid diseases, current medication, and laboratory results were recorded and analyzed. Results One hundred and sixteen patients were included, with a mean age of 27.5 ± 13.5 years, 57.8% were female, and 87.9% were transfusion dependent. Proportions of homozygous beta-thalassemia and beta-thalassemia hemoglobin E were 12.1 and 87.9%, respectively. The baseline hematocrit was 26.3 ± 3.3%. The prevalence of LVDD was 20.7% (95% CI: 13.7–29.2%). Cardiac T2* was abnormal in 7.8% (95% CI: 3.6–14.2%). Multivariate analysis revealed age, body surface area, homozygous beta-thalassemia, splenectomy, heart rate, and diastolic blood pressure to be significantly associated with LVDD. Conclusions LVDD already exists from the early stages of the disease before the abnormal heart T2 * is detected. Homozygous beta-thalassemia and splenectomy were strong predictors of LVDD. These data may increase awareness of the disease, especially in the high risk groups.