Restless Legs Syndrome (RLS) a common, under-recognized disorder disrupts sleep and diminishes quality of life. Despite a clear relation between low peripheral iron and increased prevalence and severity of RLS, the prevalence and clinical significance of RLS in iron-deficient anemic (IDA) populations is unknown. In this study all new patients referred for anemia to a community-based hematology practice over a 1-year period (March 2011–2012) were included if they had IDA and no RLS treatment. Patients completed a validated questionnaire identifying RLS, blood tests, and a sleep-vitality questionnaire (SVQ). Patients with RLS were compared to patients with no RLS for differences on SVQ, blood tests, baseline characteristics, and sleep quality. Three hundred forty-three patients were evaluated and 251 (89.2% female, average age of 45.6 years) included in the study. The prevalence of clinically significant RLS (RLS sufferers) was 23.9%, nine times higher than the general population. IDA-RLS sufferers reported poorer quality of sleep, decreased sleep time, increased tiredness, and decreased energy during the day compared to patients with IDA without RLS. Blood tests did not relate to RLS diagnosis but RLS was less likely for African-American than Caucasian patients. Clinically significant RLS occurs commonly with IDA producing much greater disruption of sleep and shorter sleep times than does IDA alone. This indicates the need for identification of RLS with IDA and consideration of appropriate therapeutic interventions for this sizeable subgroup: either aggressive iron treatment to reduce the RLS symptoms or medications for RLS or both. Am. J. Hematol. 88:261–264, 2013. © 2013 Wiley Periodicals, Inc.