To identify the relationship between pathologic electroencephalographic (EEG) patterns, clinical and neuroradiological abnormalities, and outcome in hospitalized patients with acute encephalopathy. This 5-year cohort study was performed at an academic tertiary care center. EEGs in 154 patients with altered mental status were classified according to five predefined patterns: Isolated continuous slowing of background activity (theta, theta/delta, and delta activity) and patterns with slowing background activity with episodic transients [i.e., triphasic waves (TWs) or frontal intermittent delta activity (FIRDA)]. Clinical characteristics, blood tests and neuroimaging were compared among groups. Associations between EEG patterns and structural and non-structural abnormalities were calculated. Glasgow Outcome Score >3 at discharge was defined as favorable and 1-3 as unfavorable outcome. In multivariable analyses, theta was associated with brain atrophy (OR 2.6, p = 0.020), theta/delta with intracerebral hemorrhages (OR 6.8, p = 0.005), FIRDA with past cerebrovascular accidents (OR 2.7, p = 0.004), TWs with liver or multi-organ failure (OR 6, p = 0.004; OR 4, p = 0.039), and delta activity with alcohol/drug abuse with or without intoxication, and HIV infection (OR 3.8, p = 0.003; OR 9, p = 0.004). TWs were associated with death (OR 4.5, p = 0.005); theta/delta with unfavorable outcomes (OR 2.5, p = 0.033), while patients with FIRDA had favorable outcomes (OR 4.8, p = 0.004). In encephalopathic patients, well-defined EEG patterns are associated with specific pathological conditions and outcomes, suggesting that mechanistic hypotheses underlie these abnormal EEG patterns. To clarify the respective contributions of non-structural and structural abnormalities to encephalopathy reflected in specific EEG patterns, prospective studies using continuous EEG monitoring during the acute onset of encephalopathy are needed.