Limited research suggests a relationship between restless legs syndrome and hypertension. We, therefore, assessed the relationship between restless legs syndrome and hypertension among middle-aged women. This is a cross-sectional study including 65 544 women (aged 41-58 years) participating in Nurses' Health Study II. The participants with diabetes mellitus and arthritis were excluded, because these conditions can mimic restless legs syndrome. Restless legs syndrome was assessed by a self-administered questionnaire based on the International Restless Legs Study Group criteria. Information on diagnosis of hypertension and blood pressure values were collected via questionnaires. Multivariable logistic regression models were used to analyze the relation between restless legs syndrome and hypertension, with adjustment for age, race, body mass index, physical activity, menopausal status, smoking, use of analgesics, and intake of alcohol, caffeine, folate, and iron. Compared with women with no restless legs symptoms, the multiple adjusted odds of having hypertension were 1.20 times (95% CI: 1.10-1.30; P<0.0001) higher among women with restless legs symptoms. The adjusted odds ratios for women who reported restless legs symptoms 5 to 14 times per month and ≥15 times per month were 1.06 (95% CI: 0.94-1.18) and 1.41 (95% CI: 1.24-1.61) respectively, compared with those without the symptoms (P trend: <0.0001). Greater frequency of restless legs symptoms was associated with higher concurrent systolic and diastolic blood pressures (P trend: <0.0001 for both). Women with restless legs syndrome have a higher prevalence of hypertension, and this prevalence increases with more frequent restless legs symptoms.