Purpose Factors that determine renal function after partial nephrectomy are not well- defined, including the impact of cold vs warm ischemia, and the relative importance of modifiable and nonmodifiable factors. We studied these determinants in a large cohort of patients with a solitary functioning kidney undergoing partial nephrectomy. Materials and Methods From 1980 to 2009, 660 partial nephrectomies were performed at 4 centers for tumor in a solitary functioning kidney under cold (300) or warm (360) ischemia. Data were collected in institutional review board approved registries and followup averaged 4.5 years. Preoperative and postoperative glomerular filtration rates were estimated via the Chronic Kidney Disease-Epidemiology Study equation. Results At 3 months after partial nephrectomy median glomerular filtration rate decreased by equivalent amounts with cold or warm ischemia (21% vs 22%, respectively, p = 0.7), although median cold ischemic times were much longer (45 vs 22 minutes respectively, p <0.001). On multivariable analyses increasing age, larger tumor size, lower preoperative glomerular filtration rate and longer ischemia time were associated with decreased postoperative glomerular filtration rate (p <0.05). When percentage of parenchyma spared was incorporated into the analysis, this factor and preoperative glomerular filtration rate proved to be the primary determinants of ultimate renal function, and duration of ischemia lost statistical significance. Conclusions This nonrandomized, comparative study suggests that within the relatively strict parameters of conventional practice, ie predominantly short ischemic intervals and liberal use of hypothermia, ischemia time was not an independent predictor of ultimate renal function after partial nephrectomy. Long-term renal function after partial nephrectomy is determined primarily by the quantity and quality of renal parenchyma preserved, although type and duration of ischemia remain the most important modifiable factors, and warrant further study. © 2011 American Urological Association Education and Research, Inc.