BackgroundLower-than-normal estimated glomerular filtration rate (eGFR) is associated with the risk for all-cause mortality and adverse cardiovascular events. In this regard, the role of higher-than-normal eGFR is still controversial.ObjectiveInvestigate long-term clinical consequences across the levels of eGFR calculated by the creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation among apparently healthy cardiovascular risk subjects.DesignProspective study.ParticipantsParticipants (n=1747) of a population-based screening and intervention program for cardiovascular risk factors in Finland during the years 2005–2007.Main MeasuresCardiovascular morbidity and all-cause mortality.Key ResultsOver the 14-year follow-up, subjects with eGFR ≥105 ml/min/1.73 m2(n=97) had an increased risk for all-cause mortality [HR 2.15 (95% CI: 1.24–3.73)], incident peripheral artery disease [HR 2.62 (95% CI: 1.00–6.94)], and atrial fibrillation/flutter [HR 2.10 (95% CI: 1.21–3.65)] when compared to eGFR category 90–104 ml/min after adjustment for cardiovascular and lifestyle-related risk factors. The eGFR category ≥105 ml/min was also associated with a two-fold increased mortality rate compared to the Finnish general population.ConclusionsRenal hyperfiltration defined as eGFR ≥105 ml/min/1.73 m2is a frequent and important finding in patients commonly treated in primary care. These patients should be followed closely for timely interventions, such as strict BP and blood glucose regulation.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-022-07885-8.