This cross-sectional study aimed to explore the relationship between psychosocial status, disease knowledge and adherence to deferoxamine treatment in adolescents with thalassaemia major. A purposive sample of 36 adolescents with transfusion dependence, ages 12−19 years, was recruited. A semi-structured interview and two structured questionnaires were used. In this sample, 56% were low adherence and 36% were psychologically impaired. Statistically significant factors associated with psychological impairment were: adolescents more than 16 years; low deferoxamine adherence; mean ferritin more than 2500 μg/L; family size more than six; family income equal or less than 350 Jordanian dinar and having sibling with thalassaemia. Additionally, adolescents with high level of knowledge had significantly lower scores on Pediatric Symptom Checklist.