The objective was to investigate if whole-hand mechanical stimulation (MSTIM) in the tapping-flutter frequency range induces outlasting post-stimulus changes in the hand region of the primary motor cortex. MSTIM was delivered to 12 healthy subjects for 20 min using a therapeutic stimulation device (Swisswing BMR 2000). Frequencies of 10 and 25 Hz were tested in separate sessions, and for control additionally the foot sole was stimulated at 25 Hz. Motor evoked potentials (MEPs) after single (recruitment curves) and paired-pulse transcranial magnetic stimulation (TMS) were recorded from FDI and APB muscles of the right hand. TMS assessments were carried out at baseline (T0), immediately after (T1), 30 min (T2), 1 h (T3) and 2 h (T4) after end of MSTIM. After MSTIM with 25 Hz, MEP recruitment curves were increased at all post-stimulation assessments in both muscles. The most significant effect was achieved at T3 (1 h). Intracortical inhibition was decreased within the first hour, while intracortical facilitation was increased at all post-stimulation assessments. No significant effects were found following MSTIM with 10 Hz and following foot vibration. We conclude that 20 min MSTIM with a frequency of 25 Hz induces outlasting plastic changes in the primary motor cortex. Paired-pulse stimulation further confirms that intrinsic intracortical mechanisms are involved in these changes. Spinal adaptation could be excluded (F-wave assessments). These results could be of relevance for hemiplegic patients with motor deficits, to improve the rehabilitation outcome with vibration exercise in combination with motor training.