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Cystectomy is a first line treatment for muscle invasive bladder cancer and a last resort option for several benign bladder conditions. It is currently unknown how the perioperative outcomes of cystectomy for cancer differ from those of cystectomy for benign conditions.Using the National Surgical Quality Improvement Program database we extracted data on cystectomy between 2006 and 2013. Bivariate comparison of baseline characteristics was performed and multivariate logistic regression analyses were conducted to assess the effect of cystectomy indication on 30-day outcomes.Overall 3,166 and 248 cystectomies were performed for cancer and benign conditions, respectively. Patients in the noncancer group were younger (median age 62.5 vs 70.0 years), had worse American Society of Anesthesiologists scores (3–4, 81.5% vs 73.8%) and functional health status (19.0% vs 1.6%), and more frequently had preoperative sepsis (3.2% vs 1.1%) and paresis (4.8% vs 0.3%) compared to patients in the cancer group (all values p ≤0.013). On adjusted analyses patients without cancer were more likely to experience prolonged length of stay (OR 2.14, 95% CI 1.60–2.86) and to be discharged to a special care facility (OR 3.08, 95% CI 2.13–4.47) compared to patients with cancer (all values p <0.001).Cystectomy performed for benign conditions is associated with higher odds of prolonged length of stay and adverse discharge disposition, which may be the result of worse baseline functional status and comorbid conditions. Adapting postoperative pathways after cystectomy in consideration of patients’ baseline characteristics might be one approach to mitigate such outcome differences.