Serum troponin measurement forms a cornerstone of acute myocardial infarction (AMI) diagnosis. A major challenge is interpretation of an elevated first troponin in patients with impaired renal function. We aimed to (1) evaluate the relationship between estimated glomerular filtration rate (eGFR) and first troponin, (2) characterise the performance of different troponin assays for diagnosing AMI and (3) derive eGFR-specific thresholds for potential clinical use. We analysed the distribution of troponin values stratified by eGFR and AMI. Diagnostic performance was analysed using the C-statistic. Test detection rate, false positive rate and positive predictive value were calculated for different cut-offs. We included 221 175 patients between 2010 and 2017 from four acute tertiary care hospitals in London, UK, with a median age of 65 years (IQR 49-79). eGFR was<60 mL/min/1.73 m2 in 20.6% of patients and 6.4% of patients had a diagnosis of AMI. In patients without AMI, we observed an inverse log-linear relationship between eGFR and troponin. Diagnostic performance for AMI was best in patients with eGFR>90 (C-statistic 0.93) and worst in eGFR<15 (C-statistic 0.81). For high-sensitive troponin T, using the conventional cut-off of 14 ng/L, false positive rates ranged from 68-93% for eGFRs between 15 and 60 mL/min/1.73 m2. Restricting the false positive rate to 15% yields eGFR specific cut-offs of 73, 112 and 184 ng/L, with detection rates of 73%, 70% and 68% in patients with an eGFR of 45-60, 30-45 or 15-30 mL/min/1.73 m2. The diagnostic performance of an unadjusted troponin cut-off for AMI falls with worsening renal function. We propose consideration of eGFR specific cut-offs to support more effective triage and early management of suspected AMI in patients with renal impairment. NCT03507309.