Background and Aims: Colonoscopic polypectomy in end‐stage renal disease (ESRD) patients are at risks of post‐polypectomy bleeding and perforation, but evidences are limited. This study aimed to determine the incident polypectomy complications among ESRD patients. Methods: In the nationwide ESRD cohort, a propensity score matched case–control study design was conducted to assess risk associated with post‐polypectomy bleeding and perforation using the Taiwanese National Health Insurance Research Database from 1997 to 2013 for adults aged 40 years and older; 7011 ESRD and 19 118 non‐ESRD patients met the study criteria. A total of 5302 patients in each group were matched for further analyses. The primary endpoint was post‐polypectomy bleeding or bowel perforation in 30 days. The secondary endpoint was mortality and length of hospital stay for the bleeding complications requiring hospitalization. Results: Overall incidences of post‐polypectomy bleeding or perforation in patients with ESRD was higher than the non‐ESRD group (5.83% vs 1.78%, P < 0.0001) in the matched cohort. High risk of adverse outcomes was associated with ESRD (adjusted odds ratio [aOR], 2.38, 95% confidence interval [CI], 1.85–3.05), female patient (aOR, 1.7, 95% CI, 1.37–2.11), history of acute myocardial infarction (aOR, 1.91, 95% CI, 1.1–3.32), liver disease (aOR, 1.79, 95% CI, 1.37–2.34), diabetes (aOR, 1.45, 95% CI, 1.16–1.82), cancer (aOR, 1.4, 95% CI, 1.09–1.81), inpatient setting (aOR, 13.19, 95% CI, 9.73–17.88), and prior use of clopidogrel (aOR, 1.61, 95% CI, 1.03–2.52) and warfarin (aOR, 2.03, 95% CI, 1.21–3.41). Conclusions: End‐stage renal disease was associated with approximately twofold higher risk of colonoscopic post‐polypectomy bleeding or perforation and should be cautiously performed in this special population cohort. [ABSTRACT FROM AUTHOR]