- Objective: to assess safety and efficacy of bilateral repetitive transcranial magnetic stimulation (rTMS) over the motor areas associated to motor training (MT) on upper limb (UL) motor function in chronic stroke patients. Background: the crucial role of non-primary motor cortices and contralesional brain areas for motor recovery in chronic stroke is recently emerging. rTMS could facilitate motor recovery by enhancing brain plasticity. Methods: 16 chronic stroke patients (> 6 months) were included in this study double-blind, sham-controlled prospective trial. Eleven sessions of rTMS (20 Hz at 90[percnt] of resting motor threshold-RMT) were delivered with the H-coil over the motor areas bilaterally. Subjects were randomly allocated to the real rTMS+MT (8 pz) or the sham rTMS+MT (8 pz). UL function was evaluated by the Fugl-Meyer assessment (FMA), hand grip and pinch strength at baseline (T0), one day after treatment (T1) and at one-month follow-up (T2). Motor evoked potential (MEPs) at 120[percnt] of RMT on the first dorsal interosseoum were also measured. Results: no participant reported adverse effects. At T1 both groups showed a significant improvement in FMA (sham+MT p=0,015; real+MT p=0,002) while at T2 the difference with baseline persisted only for the real+MT group (p=0,001). Furthermore, the improvement obtained for the real+MT was significantly higher than that observed for the sham+MT group (p=0.03). Patients more impaired at T0 who underwent real stimulation showed better recovery at T2 (r=−0,69 p=0,003). Grip and pinch straight improved after treatment without significant differences between groups. MEPs amplitude over the affected side significantly increased in the real+MT than the sham+MT group at T2 (p=0.01). Conclusions: we demonstrated that bilateral high-frequency rTMS with H-coil associated with MT is safe and enhances the effect of MT alone. Our data suggest that subject with a more sever motor impairment may mainly benefit from this stimulation protocol. Disclosure: Dr. Chieffo has nothing to disclose. Dr. Scopelliti has nothing to disclose. Dr. Houdayer has nothing to disclose. Dr. Di Maggio has nothing to disclose. Dr. Ferrari has nothing to disclose. Dr. Fichera has nothing to disclose. Dr. Nuara has nothing to disclose. Dr. Simone has nothing to disclose. Dr. Santangelo has nothing to disclose. Dr. Zangen has received license payments from the NIH and the Weizmann Institute. Dr. Comi has received personal compensation for activities with Teva, Novartis, Genzyme, Merck Serono, Biogen, Bayer, Actelion, Almirall, and Serono Symposia International Foundation. Dr. Leocani has received personal compensation for activities with AbbVie, Almirall, Biogen, Excemed, Genzyme, EMD Serono, and Novartis.