Background Patients with chronic kidney disease ( CKD ) are at high risk of myocardial infarction. Cardiac troponins are the biomarkers of choice for the diagnosis of acute myocardial infarction ( AMI ) without ST ‐segment elevation ( NSTE ). In patients with CKD , troponin levels are often chronically elevated, which reduces their diagnostic utility when NSTE ‐ AMI is suspected. The aim of this study was to derive a diagnostic algorithm for serial troponin measurements in patients with CKD and suspected NSTE ‐ AMI . Methods and Results Two cohorts, 1494 patients from a prospective cohort study with high‐sensitivity troponin I (hs‐ cTnI ) measurements and 7059 cases from a clinical registry with high‐sensitivity troponin T (hs‐ cTnT ) measurements, were analyzed. The prospective cohort comprised 280 CKD patients (estimated glomerular filtration rate <60 mL/min/1.73 m ² ). The registry data set contained 1581 CKD patients. In both cohorts, CKD patients were more likely to have adjudicated NSTE ‐ AMI than non‐ CKD patients. The specificities of hs‐ cTnI and hs‐ cTnT to detect NSTE ‐ AMI were reduced with CKD (0.82 versus 0.91 for hs‐ cTnI and 0.26 versus 0.73 for hs‐ cTnT ) but could be restored by applying optimized cutoffs to either the first or a second measurement after 3 hours. The best diagnostic performance was achieved with an algorithm that incorporates serial measurements and rules in or out AMI in 69% (hs‐ cTnI ) and 55% (hs‐ cTnT ) of CKD patients. Conclusions The diagnostic performance of high‐sensitivity cardiac troponins in patients with CKD with suspected NSTE ‐ AMI is improved by use of an algorithm based on admission troponin and dynamic changes in troponin concentration.