Diagnosing myocardial infarction (MI) in patients with chronic kidney disease (CKD) is difficult as they often have increased high-sensitivity cardiac troponin T (hs-cTnT) concentrations. Observational U.S. cohort study of emergency department (ED) patients undergoing hs-cTnT measurement. Cases with >1 hs-cTnT increase >99th percentile were adjudicated following the Fourth Universal Definition of MI. Diagnostic performance of baseline and serial 2-hour hs-cTnT thresholds for ruling-in acute MI was compared between those without and with CKD (eGFR <60 ml/min/1.73m2). The study cohort included 1992 patients, amongst whom 501 (25%) had CKD. There were 75 (15%) and 350 (70%) patients with CKD and 80 (5%) and 351 (24%) without CKD who had acute MI and myocardial injury. In CKD patients with baseline hs-cTnT thresholds of >52, >100, >200 or >300 ng/L, PPVs for MI were 36% (95% CI 28-45), 53% (95% CI 39-67), 73% (95% CI 50-89) and 80% (95% CI 44-98), and in those without CKD, 61% (95% CI 47-73), 69% (95% CI 49-85), 59% (95% CI 33-82) and 54% (95% CI 25-81). In CKD patients with a 2-hour hs-cTnT delta of >10, >20 or >30 ng/L, PPVs were 66% (95% CI 51-79), 86% (95% CI 68-96) and 88% (95% CI 68-97), and in those without CKD, 64% (95% CI 50-76), 73% (95% CI 57-86) and 75% (95% CI 58-88). Diagnostic performance of standard baseline and serial 2-hour hs-cTnT thresholds to rule-in MI is suboptimal in CKD patients. It significantly improves when using higher baseline thresholds and delta values.