Introduction: Current guidelines suggest using cystatin-C to confirm a reduced creatinine-based estimated glomerular filtration rate (eGFRcr) when the latter is thought to be inaccurate. Older adults have reduced muscle mass, which may affect the accuracy of eGFRcr. We evaluated the use of cystatin-C-based eGFR (eGFRcys) to confirm reduced eGFRcr among adults ≥ 80 years of age and, for comparison, younger adults. Material and methods: We analyzed data from 3,059 REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants with reduced eGFRcr (< 60 ml/min/1.73 m2) enrolled in 2003.2007 who were not on dialysis. eGFRcr and eGFRcys were calculated using age, sex and race-adjusted equations. Confirmed reduced eGFRcr was defined as eGFRcys < 60 ml/min/1.73 m2. Prevalence of chronic kidney disease complications at baseline and all-cause mortality up to March 2012 were calculated. Analyses were stratified by age: < 65, 65.79 and ≥ 80 years. Results: Among participants < 65, 65.79 and ≥ 80 years of age, 76.5%, 85.7% and 92.5%, respectively, had reduced eGFRcr confirmed with eGFRcys (p < 0.001). Among participants ≥ 80 years of age, those with reduced eGFRcr confirmed with eGFRcys had higher prevalence of hypertension (79.1% vs. 65.1%, p = 0.03) and albuminuria (38.3% vs. 22.7%, p = 0.04) and higher risk for all-cause mortality (hazard ratio: 2.43; 95% confidence interval: 1.19.5.01) as compared with those in whom reduced eGFRcr was not confirmed by eGFRcys. Conclusions: Reduced eGFRcr was confirmed using eGFRcys for the vast majority of adults ≥ 80 years. These results suggest that using cystatin-C to confirm a reduced eGFRcr may not be necessary among the oldest old.