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Introduction Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease and an important cause of end-stage renal disease. In about 20% of patients with ADPKD, native nephrectomy is performed before, after or simultaneous with a kidney transplantation. Patients with untreatable pain, recurrent infection or hematuria, suspected malignancy, pressure symptoms and lack of space to place a transplant kidney are candidates for a nephrectomy. In the literature, there is no consensus regarding the indication or timing to perform a nephrectomy. Furthermore, the optimal surgical procedure and whether to perform the nephrectomy unilateral or bilateral are not standardized. Objectives The aim of this thesis is to evaluate pre-, peri- and postoperative information of ADPKD patients who underwent native nephrectomy to establish a surgical policy for performing nephrectomy in ADPKD patients. Methods A retrospective analysis of all ADPKD patients who underwent native nephrectomy in the University Hospitals Leuven between 1 January 2008 and 1 January 2018 was performed. Postoperative complications were collected up to one year after nephrectomy and scored according to the Clavien-Dindo classification. Clinical data was compared based on type and timing of nephrectomy. Results There were 87 patients identified who underwent a total of 94 nephrectomies. Fifty-four (57.4%) nephrectomies were performed before kidney transplantation, 25 (26.6%) simultaneous and 15 (16.0%) afterwards. Of these patients, 58 (61.7%) underwent unilateral nephrectomy. The main indication was lack of space in the pretransplant and simultaneous group and infection in the posttransplant group. Patients in the bilateral group experienced a significant longer operative time compared to the unilateral group, but no differences were seen in the number of red blood cell units transfused, length of stay or in the number of admissions to the intensive care unit. The incidence of arterial hypertension decreased 14% one year after nephrectomy. The majority of complications occurred within the first three months after nephrectomy. No significant differences were seen in complication rate, timing of complications or mortality between the pretransplant and posttransplant group. Morbidity and mortality were comparable between the unilateral and bilateral group. Abdominal complications were more common in the pretransplant group, while patients in the posttransplant and unilateral group developed more complications related to the urinary tract. Multivariable analyses showed that simultaneous nephrectomy is a predictor for the development of more severe complications. Conclusion Twenty percent of ADPKD patients require nephrectomy. Pretransplant nephrectomy is most commonly performed because of lack of space for a kidney transplant. Nephrectomy patients showed a reduced need of arterial hypertension therapy. Unilateral and bilateral nephrectomy are both safe in terms of postoperative morbidity. The final decision for timing and type of nephrectomy should take into account multidisciplinary team discussion, residual kidney function and diuresis together with patient preference.