PURPOSE: To assess perioperative complications after native nephrectomy in autosomal dominant polycystic kidney disease (ADPKD), identify risk factors and evaluate surgical timing and approach. METHODS: We retrospectively analyzed 124 nephrectomy episodes in patients with ADPKD treated at a single tertiary center between October 2012 and October 2022. Complications were graded according to the Clavien-Dindo classification. Multivariable logistic regression was used to assess predictors of overall and major complications. RESULTS: Perioperative complications occurred in 73/124 episodes (58.9%), including 31 major complications (25.0%). Lower preoperative hemoglobin independently predicted overall complications (OR 0.74 per g/dL, 95% CI 0.61-0.89; p = 0.002), whereas left-sided nephrectomy was associated with a lower overall complication risk (OR 0.25, 95% CI 0.09-0.72; p = 0.011). Diverticulosis independently predicted major complications (OR 5.03, 95% CI 1.76-14.33; p = 0.003). Simultaneous bilateral nephrectomy showed the highest overall complication rate (69.7%). Open procedures were performed for markedly larger kidneys than minimally invasive procedures (median operative specimen weight 3518.5 g vs 495.5 g; p < 0.001). Minimally invasive surgery was not independently associated with a lower complication risk (OR 0.75, 95% CI 0.15-3.79; p = 0.726). CONCLUSION: Native nephrectomy in ADPKD is associated with substantial perioperative morbidity and should remain restricted to carefully selected patients. Surgical timing relative to transplantation should be guided primarily by symptoms and clinical necessity. Simultaneous bilateral nephrectomy appears to carry the greatest perioperative burden. Although minimally invasive surgery is feasible in selected patients with smaller kidneys, our data do not demonstrate an independent reduction in morbidity after adjustment for case complexity.