BACKGROUND: Transcranial magnetic stimulation (TMS) have been frequently used to explore changes in motor cortex excitability in stroke and traumatic brain injury, while the extent of motor cortex reorganization in patients with diffuse non-traumatic brain injury remains largely unknown. OBJECTIVE/HYPOTHESIS: It was hypothesized that the motor cortex excitability would be decreased and would correlate to the severity of brain injury and level of functioning in patients with anoxic, traumatic, and non-traumatic diffuse brain injury. METHODS: TMS was applied to primary motor cortices of 19 patients with brain injury (5 traumatic and 14 non-traumatic causes; on average four months after insult), and 9 healthy controls. The test parameters included resting motor threshold (RMT), short intracortical inhibition (SICI), intracortical facilitation (ICF), and short latency afferent inhibition (SAI). Excitability parameters were correlated to the severity of brain injury measured with Glasgow Coma Scale and the level of functioning assessed using the Ranchos Los Amigos Levels of Cognitive Functioning Assessment Scale and Functional Independence Measure. RESULTS: The patient group revealed a significantly decreased SICI and SAI compared to healthy controls with the amount of SICI correlated significantly to the severity of brain injury. Other electrophysiological parameters did not differ between the groups and did not exhibit any significant relationship with clinical functional scores. CONCLUSIONS: The present study demonstrated the impairment of the cortical inhibitory circuits in patients with brain injury of traumatic and non-traumatic aetiology. Moreover, the significant correlation was found between the amount of SICI and the severity of brain injury.