Abstract: This work presents the development of and clinical tests on NeReBot (NEuroREhabilitation roBOT): a three-degrees of freedom (DoF), wire-driven robot for post-stroke upper-limb rehabilitation. Basically, the robot consists of a set of 3 wires independently driven by 3 electric motors. The wires are connected to the patient’s upper limb by means of a splint and are supported by a transportable frame, located above the patient. By controlling wire length, rehabilitation treatment (based on the passive or activeassistive spatial motion of the limb) can be delivered over a wide working space. The arm trajectory is set by the therapist through a very simple teaching-by-showing procedure, enabling most common “hands on” therapy exercises to be reproduced by the robot. Compared to other rehabilitation robots, NeReBot offers the advantages of a low-cost mechanical structure, intrinsically safe treatment thanks to the use of wires, high acceptability by the patient, who does not feel constrained by an “industrial-like” robot, transportability (it can be easily placed aside a hospital bed and/or a wheelchair), and a good trade-off between low number of DoF and spatial performance. These features and the very encouraging results of the first clinical trials make the NeReBot a good candidate for adoption in the rehabilitation treatment of sub-acute stroke survivors. Clinical trials were performed with a 12-patient experimental group and a 12-patient control group. Resulted that the patients who received robotic therapy in addition to conventional therapy showed greater reductions in motor impairment (in terms of Medical Research Council score, the upper limb subsection of the Fugl-Meyer score and the Motor Status Score) and improvements in functional abilities (as measured by the Functional Independence Measure and its motor component). No adverse effects occurred and the robotic approach was very well accepted. According to these results, the NeReBot therapy may efficaciously complement standard post-stroke multidisciplinary rehabilitation and offer novel therapeutic strategies for neurological rehabilitation.