Background: Low-intensity transcranial ultrasound (TUS) is a non-invasive neuromodulation technique, which in theta burst mode (tbTUS) can increase cortical excitability. Parkinson’s disease (PD) has altered cortical excitability of motor cortex (M1). We evaluated the neurophysiological and clinical effects of M1 tbTUS in PD patients. Methods: Sixteen PD patients (4F, 59.5±9.7 years) in ON and OFF dopaminergic medication states, and 15 controls (5F, 61.9±8.7 years) were evaluated. tbTUS was applied for 80 seconds at M1 with 20W/cm2. Motor evoked potential (MEP) was recorded at baseline, at 5-minutes (T5), T30, and T60 after tbTUS. Motor (m)UPDRS was evaluated in PD at baseline and T60. Results: A linear mixed model on MEP amplitudes comparing PD-ON, PD-OFF and controls showed significant effect of time (F=4.83, p=0.003). Post-hoc analysis showed significant difference between baseline and T30 timepoints (p=0.0003). The MEP increase at T30 was higher in controls (66%), followed by PD-ON (41%) and PD-OFF (21%). PD-ON showed reduced mUPDRS at T60 when compared to PD-OFF, with significant effect of time (F=6.14, p=0.017) and group (F=5.39, p=0.025). Conclusions: tbTUS induced motor cortical plasticity is reduced in PD-OFF, that is partially restored by dopaminergic medications.Repeated sessions of tbTUS can be further investigated as a novel non-invasive treatment for PD.