BackgroundDiscrepancies have been reported in the prevalence rate of restless legs syndrome (RLS) among different ethnic groups and geographic populations. Furthermore, there are disagreements on determinant factors and associated comorbidities of RLS. We aimed to estimate prevalence of RLS and investigate its associated comorbid conditions and risk factors in a large population-based door-to-door survey.MethodsFollowing a multistage random sampling from the households lived in 22 urban districts of Tehran, Iran, 19176 participants with ≥30 years of age were recruited. Trained surveyors filled study checklist consisting of baseline characteristics, risk factors and comorbidity profile and the International RLS Study Group (IRLSSG) diagnostic criteria through face-to-face interviews.ResultsIn total, 1580 individuals were positively screened for RLS resulting in a standardized prevalence rate of 60.0/1000. There was a gradual increase in RLS prevalence by advancing age, however, sex difference disappeared after adjustment. Parkinsonism [adjusted odds’ ratio (adj-OR) = 7.4 (95% CI: 5.3–10.4)], peripheral neuropathy [adj-OR = 3.7 (95% CI: 3.3–4.1)], subjective cognitive impairment (SCI) [adj-OR = 3.1 (95% CI: 2.7–3.4)], acting out dreams [adj-OR = 2.8 (95% CI: 2.5–3.2)], hyposmia [adj-OR = 2.5 (95% CI: 2.2–2.9)], active smoking [adj-OR = 1.5 (95% CI: 1.3–1.9)] and additional number of cardiometabolic diseases associated with higher risk of RLS [adj-OR = 1.6 (95% CI: 1.2–2.3)].ConclusionOur findings showed that neuro-cognitive co-morbidities such as parkinsonism, peripheral neuropathy, SCI, acting out dreams and hyposmia as well as cardio-metabolic risk factors and diseases were independent determinants of RLS. It is recommended to screen individuals with either these comorbid conditions for RLS or the ones with RLS for the accompanying diseases.