The authors performed a prospective, controlled, 3-year, follow-up study on infections and illnesses in Hb E beta-thalassemic pediatric patients. Fifty severe and 24 non-severe patients and 24 controls were included. Siblings with an age difference of no more than 4 years served as controls. All patients and controls were asked to write postcards every two weeks to report on their illnesses and treatments. The respective median follow-up was 32.5, 35.5 and 34 months in 1501, 707 and 785 patient-months at 11.50 +/- 4.74, 10.50 +/- 4.18 and 10.75 +/- 4.56 years of age (+/- SD) for the severe, non-severe Hb E beta-thalassemic patients, and controls. The rate per 1000 patient-months of infections was not significantly different between groups despite having 26 (52%) splenectomised patients in the severe group. The infection rate among severe, non-severe, Hb E beta-thalassemic, patients and controls was not significantly different. Regular blood transfusions and iron chelation might decrease infections among Hb E beta-thalassemic, pediatric patients.