Restless legs syndrome (RLS) affects both the general population and patients with chronic renal failure. Even though it has been suggested that all forms of RLS share a common pathophysiology, not much evidence exists on how RLS of different etiology could affect aspects related to quality of life (QoL). The aim of this study was to investigate whether patients with uremic RLS (uRLS) experience lower QoL, mental health, and sleep quality, compared with their idiopathic RLS (iRLS) counterparts. Fifteen iRLS patients, 26 uRLS patients, and 15 age-matched healthy individuals participated in the study. The RLS diagnosis and severity, the depression levels, the perception of sleep, and perceived health-related QoL levels were assessed through validated questionnaires. Sleep status was not different between the two RLS groups. In contrast, the uRLS patients scored higher in RLS symptoms severity, depression, while they scored lower in QoL levels compared with iRLS patients. QoL levels were significantly lower in both RLS groups compared with healthy individuals. In conclusion, the uRLS patients experienced lower QoL levels and more severe RLS symptoms, compared with the idiopathic group, possibly leading to the observed higher depression symptoms score.