The purpose of this investigation was to document the clinical presentation of emergency department (ED) patients who tested positive for concurrent cocaine (COC) and ethanol (EtOH) use and the incidence of cocaethylene (CE) formation in this study population. Four study groups were evaluated: (1) drug-free, (2) EtOH-only, (3) COC-only, and (4) COC plus EtOH. CE was detected in plasma or urine specimens in 88% of the COC/EtOH-positive patients, and correlated directly with plasma COC and its metabolite benzoylecognine. Blood pressure and body temperature did not vary across study groups. COC/EtOH-positive patients displayed a significantly higher mean respiratory rate while the EtOH-only study group had an elevated mean heart rate. No significant differences were detected with respect to cardiac and neurological complaints between study groups. Trauma complaints in the drug-positive groups were more frequent than the incidence reported in the drug-free population. COC/EtOH-positive patients had the greatest percentage of trauma complaints (34.6%). Nearly half of the patients who tested positive for CE cited trauma as the primary reason for reporting to the ED. We conclude that ED patients who have concurrently used COC and EtOH are more closely associated with presentations related to traumatic injury than to those related to toxicologic complications.