There are few evidences on safety of Constraint-Induced Movement Therapy (CIMT), as well as its effects in neurological conditions, including multiple sclerosis (MS).To evaluate safety and effectiveness of a 2-week CIMT protocol on upper limb activity of progressive MS patients through a three-dimensional (3D) kinematic analysis.In this randomized single-blind pilot study, we randomly allocated patients affected by progressive MS reporting a reduced use of one upper limb into two different groups: CIMT group (less affected limb blocked by a splint) and control group (undergoing bi-manual treatment). Primary outcome was CIMT safety. Furthermore, we assessed CIMT effects through clinical outcomes (hand grip strength, HGS, and 9 Hole Peg Test, 9HPT) and 3D kinematic analysis (normalized jerk, number of movement units, going phase duration, mean velocity, endpoint error). All evaluations were performed at baseline (T0) and after 2 weeks of treatment (T1) for both arms in both groups.Ten MS patients, mean aged 51.0±7.7 years, were randomly allocated in the 2 groups. After treatment, no differences were found in the blocked arm. Furthermore, CIMT group showed significant improvements in clinical and kinematic parameters.CIMT might be considered a safe and effective technique in MS patients.