Despite the risk of life-threatening toxicities, care of most patients after antidepressant overdose (ADO) does not require the use of critical care resources. The use of emergency department (ED) clinical findings to identify ADO patients who subsequently manifested toxicity was evaluated prospectively. ADO risk assessment (ADORA) criteria included development of QRS interval > 0.10 seconds, arrhythmias, altered mental status, seizures, respiratory depression, or hypotension. Sixty-seven ADO patients were identified on presentation to a single ED and classified as low risk (LR, absence of criteria) or high risk (HR, presence of one or more criteria) based on development of criteria within 6 hours of ingestion (or ED presentation if ingestion time was not established). This system demonstrated 100% sensitivity in identifying study patients who developed significant toxicity problems. None of the 28 LR patients and 13 of 39 HR patients had subsequent complications (P < .01). No single clinical finding permitted risk classification. ADORA should identify patients who do not require further monitoring or other aggressive medical management for ADO.