Restless leg syndrome (RLS) is a common cause of lower extremity discomfort. We hypothesized that patients with RLS symptoms have higher rates of deep and superficial venous reflux (SVR). Retrospective review of patients ≥18 years of age evaluated in a venous center from December 2018 to February 2019. Differences in rates of RLS symptoms, demographics, comorbidities, and clinical and radiologic presence of venous disease were analyzed. Overall, 207 patients were analyzed; 140 (67.6%) reported RLS symptoms (  = 25 with prior RLS diagnosis). RLS symptoms were more common with superficial or combined superficial and deep venous reflux (DVR) compared with those without reflux (  < 0.001). Patients with RLS symptoms as opposed to those without had similar demographics and comorbidities (all  > 0.05) but increased rates of venous pain, phlebitis, family history of venous disease, lower extremity swelling and SVR, and combined SVR and DVR (all  < 0.05). Our multivariable logistic regression found presence of SVR, and family history of venous reflux was associated with RLS symptomatology (all  < 0.001). Ninety-nine patients with RLS underwent ablation; of them, 93 had duplex-proven reflux resolution of which 81 (87%) reported RLS symptom improvement. This included 13 of 16 (81.3%) with prior RLS diagnosis. SVR is associated with increased rates of RLS symptoms in a vein center population. Therefore, RLS symptoms should trigger a targeted venous evaluation. Our results suggest that venous ablation may lead to resolution of RLS symptoms in patients with SVR, but randomized prospective trials with strict RLS definition criteria are warranted to confirm these outcomes.