Laparoscopy has become the preferred method for nephrectomy in many medical centers. We compared our experience with hand-assisted laparoscopic nephrectomy (HALN) and standard laparoscopic nephrectomy (LN). Data were prospectively collected on 119 consecutive patients undergoing laparoscopic nephrectomy between August 2000 and November 2002. Outcomes were compared for LN versus HALN using Wilcoxon rank sum test for quantitative outcomes and Fisher exact test and chi2 for qualitative outcomes. Thirty-nine patients underwent LN: 16 live donor, 16 radical, and 7 simple nephrectomies. Eighty patients were treated with HALN: 47 live donor, 32 radical, and 1 simple nephrectomy. There were no differences in mean age (49.2 years LN vs. 47.7 years HALN, P = 0.60) or weight (192.2 lb LN, 179.2 lb HALN, P = 0.12). Mean tumor size (4.77 cm LN vs. 7.12 cm HALN, P = 0.07) and length of extraction incision (8.37 cm LN vs. 7.87 cm HALN, P = 0.08) were similar. Total hospital charges (19,352 dollars vs. 18,505 dollars, P = 0.29) and length of stay (3.68 days vs. 3.72 days, P = 0.15) were equivalent for LN and HALN. Average operative time for HALN was significantly shorter (202 minutes vs. 258 minutes, P = 0.0001), and blood loss was less for HALN (71.7 cc vs. 113.1 cc, P = 0.007). Wound complications rates were similar (6.5% HALN vs. 13% LN, P = 0.34), but overall morbidity rates were higher after LN (28.2% vs. 6.3%, P = 0.001). Compared with pure laparoscopic nephrectomy, the hand-assisted approach reduces operative time and blood loss without increasing total hospital charges or length of stay. In our patients, HALN was also associated with fewer postoperative complications than standard laparoscopic nephrectomy. Hand-assisted laparoscopy may allow for the performance of increasingly complex procedures while maintaining the benefits of minimally invasive surgery.