Invasive electroencephalography (EEG) monitoring is often needed for presurgical evaluation in patients with medically intractable epilepsy (MIE). This study retrospectively reviews the pathologic changes associated with EEG monitoring. Two hundred twenty-six patients who underwent invasive monitoring (53.5% males; mean age, 29.8 years) and 55 controls without EEG monitoring (52.7% males; mean age, 25.6 years) were evaluated. Median length of invasive EEG monitoring was 7.0 days. Compared with controls, patients who were monitored had more pathologic changes related to invasive EEG monitoring (n = 171 [75.7%] vs n = 12 [21.8%]; P < .0001) including meningeal or parenchymal chronic inflammation (n = 128 [56.4%] vs n = 11 [20.4%]; P < .0001) and acute contusion and/or acute/subacute infarct (n = 110 [48.5%] vs n = 0; P < .0001). Histologic evidence of pathologic changes typically associated with invasive monitoring and/or craniotomy occurred in 76% of our patients with invasive monitoring compared with 19% in patients without prior invasive EEG evaluation. The most common pathologic changes related to invasive monitoring were chronic inflammation and contusion/infarct.