Summary Purpose:  We used transcranial magnetic stimulation (TMS) to investigate cortical excitability changes in Lennox‐Gastaut syndrome (LGS), anticipating we would find a marked increase in excitability compared to other patients with refractory epilepsies. Methods:  Eighteen patients with LGS were studied. Motor threshold (MT), short intracortical inhibition (paired pulse TMS at 2 and 5 msec interstimulus intervals ISIs), intracortical facilitation (10 and 15 msec ISIs), and long intracortical inhibition (100–300 msec ISIs) were measured. Results were compared to those of 20 patients with chronic refractory idiopathic generalized epilepsy (IGE), 20 patients with chronic refractory focal epilepsy, and 20 healthy nonepilepsy controls. Key Findings:  A significant decrease in cortical excitability was observed in LGS compared to the other two groups with refractory epilepsy as evidenced by increased MT and intracortical inhibition at both short (2, 5 msec ISIs), and long (100–300 msec ISIs) as well as decreased intracortical facilitation (10, 15 msec ISIs), (p < 0.01; effect sizes ranging from 0.3 to 1.8). Cortical excitability was also lower in LGS compared to nonepilepsy controls (increased MT and decreased intracortical facilitation; p < 0.05; effect sizes ranging from 0.5 to 0.9). Significance:  Interictal cortical excitability is decreased in LGS; a feature that distinguishes it from other refractory epilepsy syndromes. This decrease may be an important mechanism for the neurobehavioral comorbidities associated with LGS.