Autosomal dominant polycystic kidney disease (ADPKD) is often characterized by end-stage renal disease (ESRD) and problems including pain, hematuria, and infection. Open nephrectomy is curative; however, the morbidity of the procedure is considerable. Between 1995 and 1998, 11 laparoscopic nephrectomies were performed on nine symptomatic patients (five men and four women) with ESRD and ADPKD. Two patients underwent a staged bilateral laparoscopic nephrectomy. All patients presented with abdominal or flank pain and an abdominal mass. Other clinical problems included hypertension in eight patients, urinary tract infections in two patients, and gross hematuria in one patient. Seven patients were receiving long-term dialysis treatment, and two patients had undergone prior renal transplantation. Patients were evaluated for preoperative and postoperative pain, analgesic use, hospital course, and convalescence. The overall average operative time was 6.3 hours, with an average estimated blood loss of 153 mL. Eight nephrectomy specimens were removed by morcellation, and three specimens were removed intact through a 7- to 12-cm incision. The average hospital stay was 3 days, and the average time to normal activity was 5 weeks. With a mean follow-up of 31 months, all nine patients reported elimination of their preoperative pain based on a pain analogue score. Six major and two minor complications occurred, including blood transfusion, a vena cavotomy, splenic cyanosis, pulmonary embolism, clotted arteriovenous fistula, and brachial plexus injury. Incisional hernias occurred in two of the three patients who underwent open removal. One patient noted improvement, and two patients noted resolution of their hypertension postoperatively. Laparoscopic nephrectomy in patients with ADPKD and ESRD offers an effective alternative to open nephrectomy to manage renal-related pain. This procedure provides the benefits of minimal intraoperative blood loss, minimal postoperative pain, brief hospital stay, and rapid convalescence.