Live kidney donors have an increased risk of ESRD compared with nondonors; however, it is unknown whether undetected, subclinical kidney disease exists at donation that subsequently contributes to this risk. To indirectly test this hypothesis, we followed the donated kidneys themselves, by comparing outcomes of 257 recipients whose donors subsequently developed ESRD with a matched cohort whose donors remained ESRD-free. The compared recipients were matched on donor (age, sex, race/ethnicity, donor/recipient relationship), transplant (HLA mismatch, peak-PRA, previous transplant, year-of-transplant), and recipient risk factors (age, sex, race/ethnicity, body-mass index, cause of ESRD, and time-on-dialysis). Median recipient follow-up was 12.5 years (interquartile range 7.4–17.9, maximum 20 years). Recipients of allografts from donors who developed ESRD had increased death-censored graft loss (74% vs. 56% at 20 years; adjusted hazard ratio [aHR] 1.7; 95% confidence interval [CI] 1.5–2.0; p<0.001) and mortality (61% vs. 46% at 20 years; aHR 1.5; 95% CI 1.2–1.8; p<0.001) compared with matched recipients of allografts from donors who did not develop ESRD. This association was similar among related, spousal, and unrelated nonspousal donors. These findings support a novel view of the mechanisms underlying donor ESRD: that of pre-donation kidney disease. However, biopsy data may be required to confirm this hypothesis.