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Adherence to long-term treatment is challenging. Deferasirox (DFX) is a daily oral iron chelator approved in the United States for transfusional iron overload.Twenty-one subjects with sickle cell disease (mean age 13.8±4.2 y) received DFX 20 to 30 mg/kg daily for 1-year while on chronic blood transfusions. Good adherence to DFX was defined as ≥80% intake of prescribed dose. Adherence was assessed by monthly pill counts and calendars, and questionnaires at 1, 3, 6, and 12 months follow-up.Fifteen of 21 subjects (71%) were adherent to DFX according to self-reports, with 83% of the patients being adherent at 1 month, 89% at 3 months, 65% at 6 months, and 78% at 12 months. We were only able to document continuous good adherence in 43% of patients by pill counts because of poor bottle return. The discrepancy between pill counts and self-reports may be related to over-reporting, with the real adherence being lower. Parental involvement with DFX administration (P=0.03) and age ≤16 years (P=0.0055) correlated with adherence. We could not detect a significant correlation between serum ferritin declines and adherence.Seventy-one percent of patients adhered to DFX according to questionnaire responses but only 43% did according to pill counts. Adherence was poorer in adolescents older than 16 years of age and in patients who had no parental supervision of medications.