Hand-assisted techniques facilitated dissemination of the laparoscopic approach in live kidney donors and addressed concerns regarding potential procedural complications. We report our experience with both standard and hand-assisted laparoscopic nephrectomy in routine, complicated, and higher-risk donors. From July 1999 to September 2002, 47 donors underwent standard laparoscopic donor nephrectomy (SLDN; n = 29) or hand-assisted laparoscopic donor nephrectomy (HALDN; n = 18). Donors were "complicated" if they were > 60 years of age, obese, refused blood-product transfusion, had multiple renal arteries or veins, or had right nephrectomies. "Higher-risk" donors had two or more risk factors. Results for SLDN and HALDN were compared for the overall groups and for the "complicated" and "higher-risk" groups. No donor required blood transfusion or reoperation. Warm-ischemia times were shorter in left nephrectomies (191 +/- 72 seconds vs. 337 +/- 95 seconds, P = 0.005), and blood loss was greater in patients with a body mass index > or = 30 kg/m2 (296 +/- 232 mL vs. 170 +/- 139 mL, P = 0.03). Higher-risk donors had an increased operative blood loss and longer hospital stay than low-risk donors. Mean donor creatinine at discharge was 1.19 +/- 0.2 mg/dL. Comparison of SLDN versus HALDN revealed shorter operating times for the latter, which approached statistical significance. Warm-ischemia time, operative blood loss, length of hospitalization, and donor and recipient discharge creatinines were similar for both groups. Laparoscopic donor nephrectomy can be applied to selected higher-risk donors with outcomes comparable to uncomplicated donors. Hand-assisted techniques facilitate the procedure during the learning curve, with advantages similar to standard laparoscopic techniques.