Introduction: Thalassemia is one of the most common worldwide genetic disorders in which there are overgrowth of the skull, rodent face, protrusion and spacing of maxillary anterior teeth, open bite, progressive reduction of bone mass, retardation in general skeletal growth and teeth development are there (exists). Quantitative assessments of the skeletal morphology of patients with thalassemia major are rare therefore, the purpose of this study was to evaluate cephalometric skeletal and dental features, dental arch dimensions and teeth development in relation to bone mineral density and vitamin D in a group of Egyptian patients with thalassemia major relative to healthy control age and gender matched. Patients and Methods: This study was carried on 94 thalassemia patients (46 male and 48 female) compared with 120 subjects (age and gender matched healthy control 60 male and 60 female). Age ranged from 6 to 12 year. For each patient some cephalometric skeletal and dental measurements, dental arch dimensions, vitamin D, DXA scan to measure bone mineral density and dental age was done. Results: All thalassemic patients had a significant hyper-divergent growth pattern leading to steep mandibular plane, increased anterior facial height and decreased posterior facial height, Short mandibular body, short ramus length, shorter arch width and shorter arch circumference when compared with healthy control, Class II malocclusion with an average ANB angle of 7.5 degree. The retardation of dental development in thalassemic male and female equal to (1.011 and 0.791 year) respectively. Thalassemic male showed significant negative correlation between (CA-DA) and BMD. Conclusions: In all thalassemic patient skeletal Class II dental base relation, shorter dental arch dimensions significant retardation in dental age, very low level of vitamin D and reduced bone mineral density had found.