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Comprehensive medical care of patients with sickle cell disease decreases morbidity, mortality, and health care resource utilization. Nonadherence to comprehensive care is a barrier to further improvement in the outcomes of these patients. We investigated the feasibility and acceptability of telephone-delivered structured follow-up, support, and education provided by nonmedical personnel and its impact on adherence to comprehensive measures. A semistructured script was designed that included a series of questions relating to the patient's well-being and health-related behaviors and was administered by a graduate student researcher in genetics. Families of all 202 children followed at Children's Hospital of Pittsburgh were attempted to be contacted at 3 monthly intervals from their last contact. A total of 76%  of those called were available and willing to talk. Eighteen months after initiation of the study, the number of patients who had not attended comprehensive care clinic for 2 years or more decreased from 46 (19.7%) to 23 patients (9.9%) (P = 0.0019). Similarly, the proportion of eligible patients who had undergone transcranial Doppler screening within the past 12 months increased from 34 to 49% (P = 0.0501). Structured telephonebased follow-up is feasible and well accepted and can lead to improved adherence with comprehensive care measures.