Despite the fact that multiple sclerosis (MS) patients often include leg restlessness as a sensory symptom, MS is not mentioned amongst symptomatic restless legs syndrome (RLS) forms. The aim of this study was to estimate RLS prevalence in a large population of MS patients, comparing clinical and MRI findings between patients with and without RLS. Each of the 156 MS patients (100 females, 56 males, mean age 40.7 ± 10.4) enrolled in a prospective study underwent a medical history interview, a neurological examination with the assessment of the Expanded Disability Status Scale (EDSS), and a structured questionnaire to verify the presence and features of RLS. Conventional brain–spinal MRIs of 99 subjects were also evaluated and compared between patients with and without RLS. Fifty-one subjects (32.7%) (mean age 43.8 ± 12.8) met the criteria for RLS. In a few patients (8.5%), the RLS preceded clinical MS onset, whilst in the remaining cases the RLS was followed by or was simultaneous with clinical MS onset. Comparing the RLS group with the group without RLS, no significant differences were found in MS duration, gender, and referred sleep habits. The primary progressive MS course was more represented in the RLS group, which also showed a higher EDSS score. RLS is a very common finding in MS patients and should be considered amongst the symptomatic RLS forms. RLS is also associated with higher disability.