Patients with nontransfusion-dependent thalassemia (NTDT) do not require regular blood transfusion for survival but may encounter several complications that contribute to morbidity and mortality. We report the molecular heterogeneity and hematological features of NTDT in 312 adult patients in northeast Thailand. Hemoglobin (Hb) and DNA analyses identified 177 subjects with Hb E-β-thalassemia, 1 with homozygous β⁰-thalassemia and 134 with Hb H, AEBart's and EEBart's diseases. For β-thalassemia, 12 different mutations including both β⁰- and β+-thalassemias were detected. Coinheritance of α-thalassemia as an ameliorating factor was observed in 18 of 178 cases (10.1%) with β-thalassemia. The α-globin gene triplicated haplotype (αααanti3.7) was observed in 1 case of Hb E-β⁰-thalassemia. The presence of the -158 (C→T) Gγ-Xmn I polymorphism (+/+) was found to be associated with increased Hb F expression, but its frequency in the studied subjects was low. Those with α-thalassemia included 17 with deletional and 51 nondeletional Hb H, and 63 with AEBart's and 3 with EEBart's diseases. The hematological parameters of these NTDT and genotype-phenotype relationships are presented. The diverse molecular heterogeneity of NTDT underlines the importance of complete genotyping of the patient. These results should prove useful for management planning, the prediction of clinical outcome and to improve genetic counseling for NTDT patients.