To assess the infection risk of splenectomized persons with hemoglobinopathies in Australia.This was an Australia cohort study of infections and vaccinations in 63 patients with hemoglobinopathies followed longitudinally from 1967 to 2006, and an investigation into the risk factors for poor outcome.There were 28 cases of bacterial infection that necessitated hospitalization in the cohort, resulting in an incidence of 1.4 bacterial infections per 100 patient-years. There was one death (1.6%) as a direct result of bacterial infection. Hepatitis C was diagnosed in 28 patients (44%). The spectrum of infection included pneumonia (6/28), cellulitis (6/28), bacteremia (4/28), and skin abscess (3/28). Notably, Klebsiella species organisms were isolated in 9/28 cultures.Infectious complications in this group of patients cause serious morbidity and mortality. This cohort may be a target for novel preventive strategies such as more immunogenic vaccines, patient registries, and/or education programs.