This study investigated the effect of a long-term transcutaneous electrical nerve stimulation (TENS) treatment on cortical motor representation in patients with multiple sclerosis (MS). In this double blind crossover design, patients received either TENS or sham stimulation for 3 weeks (1 hour per day) on the median nerve region of the most impaired hand, followed by the other stimulation condition after a washout period of 6 months. Cortical motor representation was mapped using transcranial magnetic stimulation (TMS) at baseline and after the 3-week stimulation protocol. Our results revealed that three weeks of daily stimulation with TENS significantly decreased the cortical motor representation of the stimulated muscle in MS patients. Although the mechanisms underlying this decrease remain unclear, our findings indicate that TENS has the ability to induce long-term reorganization in the motor cortex of MS patients.