Introduction : The purpose of this research project is to evaluate the usefulness of virtual reality (VR) environments as a tool in gait training of individuals with multiple sclerosis (MS). MS is a chronic and progressive neurological disease and its clinical course can lead to severe disability. VR is a relatively new tool in the field of neuro-rehabilitation that has many advantages including the possibility to have a complete variable control management, to monitor motor level achieved by the individual through exercises, to provide challenging and engaging exercises, to run intensive training, but in a protected environment and then to provide feedback to facilitate motor learning. Methods : Ten subjects (9 females) affected by MS (mean age 40.6, range 24-60) were studied. Two patients dropped out due to transportation and family problems, these two individuals participated only to the evaluation session and never started the training and one did not participate at the last follow up. All patients had an EDSS score between 3 and 5.5 and all were treated with natalizumab or azathioprine. Clinical evaluation included the “Six minute walk test”(6MWT), the “Timed up and go test” (TUG), the “Four Square Step Test” (FSST), the “10 meter test” and the Berg Balance Scale Test (BBS). A repeated measures design was used with evaluations at 1 week pre training (pre), one week post training (post) and at one month (post_1) and three months (post_3) follow up. Kinematic and kinetic gait analysis was used to quantify gait performance using a six camera stereophotogrammetric system (Vicon T20) and the Davis marker set with two embedded force platforms (AMTI, Watertown, MA, USA). Subjects were asked to walk under usual gait conditions and during a cognitive dual task condition of serially subtracting the number three from a three digit predefined number. For the delivery of the VR training, inertial sensors (X-SENS) were used for the acquisition of orientation of the feet. Training consisted of having subjects walk on a treadmill while negotiating virtual obstacles and a virtual environment through stereoscopic glasses or on a computer screen. Training was individualized to fit the patients needs and was provided for twelve sessions (twice a week for six weeks) for a total of 45 minutes each session and consisted of three bouts of walking of ten minutes each, with breaks in between of approximately 5 minutes rest. Level of complexity and progression was increased if the individual was able to achieve success in task performance of 80%. Progression included increasing the speed of walking on the treadmill and increasing the complexity of the VR tasks (numbers of bifurcation, obstacles distracters etc). Results: No adverse events were observed during the training. After training improvements on most motor functions were observed. Endurance as measured by the distance walked over 6 minutes improved by an average of 23 meters post training and continued to show improvement at follow up (of 70.75 m from baseline). The results show an improvement of gait and balance with a decrease of fall risk confirming the relevance of rehabilitation in MS patients. Discussion: Overall the group responded positively to the VR intervention. We observed that all improvements gained were not only stable after three months follow up, but further implemented; although it is likely that the improvements gained are to be related to VR systems a control group is needed to verify our hypothesis. This is a preliminary study aimed to determine the efficacy of a VR system and the results are very encouraging to those who hope to use VR with MS patients as a form of therapy.