Acute aortic syndrome (AAS) comprises acute aortic dissection, intramural hematoma, and penetrating ulcer of the aorta. The importance of accurate, rapid diagnosis and intervention for AAS is underscored by its clinical and epidemiologic overlap with acute coronary syndrome and by the risks of inappropriate treatment with antithrombotic agents. To explore these concerns, the recognition, management, and outcomes of AAS in the contemporary experience of a tertiary referral center were reviewed. Sixty-six consecutive patients with AAS admitted from January 2000 to December 2004 were identified, and their records reviewed. Misdiagnosis occurred in 39% (n = 26) and was associated with longer time to correct diagnosis (mean +/- SEM 51 +/- 12 vs 15 +/- 5 hours, p = 0.003). Acute coronary syndrome was the most common misdiagnosis, resulting in inappropriate treatment with acetylsalicylic acid in 26 (100%), clopidogrel in 1 (4%), heparin in 22 (85%), and fibrinolytic agents in 3 (12%). Exposure to antithrombotic agents was associated with higher rates of major bleeding (38% vs 13%) and a trend toward greater in-hospital mortality (27% vs 13%) (p = 0.02 for combined end point). Antithrombotic agent administration was also associated with increased hemorrhagic pericardial fluid (50% vs 25%), hemorrhagic pleural effusion (15% vs 3%), and hemodynamic instability (30% vs 13%) (p = 0.02 for combined end point). In conclusion, AAS is frequently confused with acute coronary syndrome, leading to delayed diagnosis and clinically significant bleeding as a consequence of inappropriate treatment with antithrombotic agents.