OBJECTIVES: We sought to evaluate the association between discordant cardiac marker results and in-hospital mortality and treatment patterns in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS). BACKGROUND: Creatine kinase-MB (CK-MB) and cardiac troponins (cTn) are often measured concurrently in patients with NSTE ACS. The significance of discordant CK-MB and cTn results is unknown. METHODS: Among 29,357 ACS patients in the CRUSADE initiative who had both CK-MB and cTn measured during the first 36 hours, we examined relationships of four marker combinations (CK-MB-/cTn-, CK-MB+/cTn-, CK-MB-/cTn+, and CK-MB+/cTn+) with mortality and American College of Cardiology/American Heart Association guidelines-recommended acute care. RESULTS: The CK-MB and cTn results were discordant in 28% of patients (CK-MB+/cTn-, 10%; CK-MB-/cTn+, 18%). In-hospital mortality was 2.7% among CK-MB-/cTn- patients; 3.0%, CK-MB+/cTn-; 4.5%, CK-MB-/cTn+; and 5.9%, CK-MB+/cTn+. After adjustment for other presenting risk factors, patients with CK-MB+/cTn- had a mortality odds ratio (OR) of 1.02 (95% confidence interval [CI] 0.75 to 1.38), those with CK-MB-/cTn+ had an OR of 1.15 (95% CI 0.86 to 1.54), and those with CK-MB+/cTn+ had an OR of 1.53 (95% CI 1.18 to 1.98). Despite variable risk, patients with CK-MB+/cTn- and CK-MB-/cTn+ were treated similarly with early antithrombotic agents and catheter-based interventions. CONCLUSIONS: Among patients with NSTE ACS, an elevated troponin level identifies patients at increased acute risk regardless of CK-MB status, but an isolated CK-MB+ status has limited prognostic value. Recognition of these risk differences may contribute to more appropriate early use of antithrombotic therapy and invasive management for all cTn+ patients.