Context.—Evaluating nontumor portions of tumor nephrectomies is useful to diagnose nonneoplastic renal disease.Objective.—To determine the medical renal disease frequency and to assess the prognostic significance of the various renal pathologic variables with long-term follow-up in tumor nephrectomy patients.Design.—We reviewed nonneoplastic kidney sections of 456 consecutive cases from 1998 to 2008. Seventy-five cases were excluded (19 tumor compression, 25 no nonneoplastic tissue, 22 embolized kidneys, 9 end stage). Special staining, immunofluorescence, and/or electron microscopy was performed where appropriate. Vascular sclerosis was scored from mild to severe; interstitial fibrosis/tubular atrophy and global glomerulosclerosis (GS) were expressed as percentages. Follow-up, minimum 12 months, was evaluated in 156 cases. All renal pathologic variables were compared with regard to change in creatinine level from preoperative assessment to follow-up.Results.—Of 381 cases, 57 had additional medical renal disease (15%), most frequently diabetic nephropathy (28) and hypertensive nephropathy (11). Postoperative creatinine levels increased significantly in patients with severe arteriosclerosis or arteriolosclerosis, >5% GS, and >10% interstitial fibrosis/tubular atrophy. Seventy-four percent of cases with additional nonneoplastic diagnoses showed severe arteriolosclerosis. Higher corresponding GS was seen in the more affected vascular cases: mean, 5.56% GS for mild versus 23% GS for severe. Three patients progressed to renal failure 1 to 4 years after nephrectomy, 2 with hypertensive nephrosclerosis and 1 with diabetic nephropathy.Conclusions.—Medical renal disease was identified in 15% of tumor nephrectomy specimens. The degrees of vascular sclerosis, GS, and interstitial fibrosis/tubular atrophy are predictive of elevated creatinine levels in postnephrectomy patients. Prognostic implications of the nontumor pathology are important in nephrectomized patients.