Background: Controversy exists about the impact of ischemia on renal function. We evaluated the creatinine clearance of patients having undergone laparoscopic renal extirpative and ablative surgery. Study Design: The records of patients undergoing laparoscopic procedures for renal masses from February 2000 to March 2004 were examined. Creatinine clearance (CrCl) for each patient was determined using the Cockcroft-Gault equation and ideal body weight. We compared CrCl changes of patients undergoing laparoscopic partial nephrectomy (without renal ischemia [LPN-none], with warm ischemia [LPN-warm], and with cold ischemia [LPN-cold]) with patients undergoing laparoscopic radical nephrectomy (LRN) and laparoscopic cryoablation. Patients predisposed to medical renal disease were substratified and evaluated. Results: All patients who underwent LRN or LPN-warm sustained a significant drop in CrCl on the first postoperative day, compared with patients who had LPN without ischemia or cryoablation (p < 0.01). The CrCl decrease correlated directly with warm ischemia time. Six months postoperatively, CrCl changes were no longer significant. Patients with medical renal disease risk factors were more likely to sustain longterm (1 year postoperatively) renal damage if they had renal ischemia, trending toward statistical significance. Conclusions: Ischemia causes acute renal damage, which is apparently reversible in patients without evidence of medical renal disease. Patients with known medical renal disease have substantial longterm changes in renal function associated with unilateral renal ischemia. Considering the insensitivity of creatinine-based renal function metrics, only eliminating ischemic time will realize the goal of maximal nephron preservation, particularly in patients with preexisting medical renal disease.