Background: Novel creatinine-based equations have recently been proposed but their predictive performance for cardiovascular outcomes in participants at high cardiovascular risk in comparison to the established CKD-EPI 2009 equation is unknown., Method: In 9361 participants from the United States included in the randomized controlled SPRINT trial, we calculated baseline estimated glomerular filtration rate (eGFR) using the CKD-EPI 2009, CKD-EPI 2021, and EKFC equations and compared their predictive value of cardiovascular events. The statistical metric used is the net reclassification improvement (NRI) presented separately for those with and those without events., Results: During a mean follow-up of 3.1 ± 0.9 years, the primary endpoint occurred in 559 participants (6.0%). When using the CKD-EPI 2009, the CKD-EPI 2021, and the EKFC equations, the prevalence of CKD (eGFR <60 ml/min/1.73 m 2 or >60 ml/min/1.73 m 2 with an ACR ≥30 mg/g) was 37% vs. 35.3% ( P = 0.02) vs. 46.4% ( P < 0.001), respectively. The corresponding mean eGFR was 72.5 ± 20.1 ml/min/1.73 m 2 vs. 73.2 ± 19.4 ml/min/1.73 m 2 ( P < 0.001) vs. 64.6 ± 17.4 ml/min/1.73 m 2 ( P < 0.001). Neither reclassification according to the CKD-EPI 2021 equation [CKD-EPI 2021 vs. CKD-EPI 2009: NRIevents: -9.5% (95% confidence interval (CI) -13.0% to -5.9%); NRInonevents: 4.8% (95% CI 3.9% to 5.7%)], nor reclassification according to the EKFC equation allowed better prediction of cardiovascular events compared to the CKD-EPI 2009 equation (EKFC vs. CKD-EPI 2009: NRIevents: 31.2% (95% CI 27.5% to 35.0%); NRInonevents: -31.1% (95% CI -32.1% to -30.1%))., Conclusion: Substituting the CKD-EPI 2009 with the CKD-EPI 2021 or the EKFC equation for calculation of eGFR in participants with high cardiovascular risk without diabetes changed the prevalence of CKD but was not associated with improved risk prediction of cardiovascular events for both those with and without the event., Competing Interests: I.E.E. received speaker honoraria from Pharmacosmos, Astellas, Bristol Myers Squibb, AstraZeneca, and Novartis. M.B. is supported by the Deutsche Forschungsgemeinschaft (German Research Foundation; TTR 219, project number 322 900 939) and reports personal fees from Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Servier, Medtronic, Vifor, Novartis, and Abbott. F.M. is supported by Deutsche Gesellschaft für Kardiologie (DGK), Deutsche Forschungsgemeinschaft (SFB TRR219), and Deutsche Herzstiftung. He has received scientific support from Ablative Solutions, Medtronic, and ReCor Medical and speaker honoraria/consulting fees from Ablative Solutions, Amgen, Astra-Zeneca, Bayer, Boehringer Ingelheim, Inari, Medtronic, Merck, ReCor Medical, Servier, and Terumo. F.G. is supported by Deutsche Herzstiftung and received speaker honoraria from AstraZeneca. L.L. has received speaker honoraria from ReCor Medical and Medtronic. M.K., J.W.P., R.K., V.P., and G.H.H. declare no competing interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)