The suppression of erythropoiesis by Hydroxyurea (HU) therapy is associated with increase in mean corpuscular volume, in addition to the increase in Hb F. Monitoring the mean corpuscular volume values and the presence of macrocytosis are effective tools of adherence to the treatment with HU in patients with sickle cell anemia. The aim of this study is to monitor the mean corpuscular volume values after starting treatment with HU to determine if macrocytosis can be used as a surrogate marker of compliance with therapy. We conducted a prospective cohort study over one year with measurements of blood counts and mean corpuscular volume after starting therapy with HU in 95 patients with sickle cell anemia who were regularly followed in our ambulatory outpatient unit. In one-year of successful use of HU the mean value of the mean corpuscular volume increased significantly. The Andersen and Gill model demonstrated that the increase of one unit of MCV implies a 5% reduction in the risk of visiting the emergency room. Monitoring mean corpuscular volume values after prescribing HU alerts the provider of noncompliance in order to counsel the patient in question for better adherence to the use of HU that could improve the quality of care and to reduce morbidity and the frequency of acute pain crises and associated healthcare costs.Universidade Estadual Paulista Júlio de Mesquita Filho, Departamento de Biologia, Instituto de Biociências Letras e Ciências Exatas de São José do Rio Preto, Sao Jose do Rio Preto, Rua Cristóvão Colombo, 2265, Jardim Nazareth, CEP 15054-000, SP, BrasilUniversidade Estadual Paulista Júlio de Mesquita Filho, Departamento de Biologia, Instituto de Biociências Letras e Ciências Exatas de São José do Rio Preto, Sao Jose do Rio Preto, Rua Cristóvão Colombo, 2265, Jardim Nazareth, CEP 15054-000, SP, BrasilHEMORIO-State Institute of Hematology Arthur de Siqueira Cavalcanti, Rio de Janeiro, BrazilFederal University of Rio de Janeiro, COPPE - Postgraduate School of Engineering, Rio de Janeiro, BrazilFederal University of Rio de Janeiro-School of Medicine, Rio de Janeiro, BrazilUNESP - Sao Paulo State University, Department of Biology, Hemoglobin and Hematologic Diseases Genetic Laboratory, São Paulo, BrazilUFF - Fluminense Federal University, Department of Clinical Medicine, School of Medicine, Niterói, BrazilCardeza Foundation, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA