Background <p>Progressive supranuclear palsy (PSP) is a rare neuro-degenerative disease. The Deep Transcranial Magnetic Stimulation (DTMS) has been proposed as a therapeutic approach in Parkinson’s Disease but there are few studies that have evaluated its efficacy in PSP.</p> Aim and Methods <p>This was a pilot, randomized, cross-over, double blind trial, with the aim to evaluate the effect of DTMS on motor functions, freezing of gait, and cognitive performance in patients with PSP. Nineteen subjects were recruited and randomly assigned to one of the study sequences: real-sham or sham-real. Each cycle consisted of 12 sessions of high frequency DTMS over a 4-week period, separated by a 5-week wash-out period. The targets were the motor cortex and the dorsolateral prefrontal cortex.</p> Results <p>After adjusting for baseline scores, an interaction effect between DTMS and&#xa0;period of administration emerged for the PSP scale; it was estimated that the real&#xa0;treatment applied to the first period induced a decrease of about 0.79 points (p=0.41)&#xa0;and 4 point (p=0.01) when administered in the second period. Improvement in gait and&#xa0;be relevant since early falls and gait dysfunction have a great impact on disability.&#xa0;Patients and caregivers appreciated the improvements but for a short period of time&#xa0;(about a week).</p> Conclusion <p>This is the first crossover, double blind, randomized clinical trial to use&#xa0;DTMS in patients with PSP. DMTS was associated with a motor and non-motor&#xa0;improvement in PSP patients.</p> Trial registration <p>clinicaltrial.gov: NCT02734485</p>