Objectives: To compare laparoendoscopic single-site (LESS) Pfannenstiel donor nephrectomy with a contemporary series of standard laparoscopic (SL) donor nephrectomies. Methods: The initial 6 LESS donor nephrectomies were compared with a case-matched 6 SL donor nephrectomies within the same time period (June 2008 till March 2009). Patient characteristics (sex, age, body mass index, graft volume, and vascular anatomy), perioperative data (operative time, warm ischemia time [WIT], and estimated blood loss), and postoperative information (complications, length of stay, visual analog scale [VAS], and total morphine requirements) were collected prospectively and analyzed retrospectively. Results: In the LESS group, there were no conversions to SL or open. There was no significant difference between the two groups in terms of baseline characteristics (age, body mass index, allograft volume). However, SL group included more right-sided patients (three compared with one) and more venous anomalies (retrorenal veins in two patients and multiple veins in another). There was no significant difference between SL and LESS in terms of operative time (117 vs. 142 minutes), WIT (5 minutes in both groups), estimated blood loss (150 vs. 100mL), median length of stay (2 days in both), and total morphine equivalents (42 vs. 83mg). None of the patients received transfusions perioperatively. A patient in the SL group developed a wound infection requiring packing and antibiotics. There were no perioperative complications in the LESS group. Although VAS scores were lower in the LESS versus SL group at each of post-operative day (POD) #2 (1.5 vs. 4) and discharge (0 vs. 2), this did not reach statistical significance. Conclusions: In this small retrospective series, SL was associated with more complex renal anatomy. However, there was no difference between the two groups in terms of WIT, narcotic requirements, and VAS scores. Therefore, the advantages of LESS may only be cosmesis. To verify these results, both procedures need to be compared prospectively in a randomized fashion. © 2010, Mary Ann Liebert, Inc.