['To compare perioperative patient safety outcomes of minimally invasive cystectomy (MIC) with open cystectomy (OC) in a national cohort. Comparative outcomes data based on validated metrics are sparse for MIC, an emerging treatment for bladder cancer.', 'We identified patients undergoing MIC and OC for bladder cancer from 2005 to 2010 using the US Nationwide Inpatient Sample. We compared perioperative outcomes using Patient Safety Indicators (PSIs), validated metrics developed by the Agency for Healthcare Research and Quality, and used multivariate regression analyses to generate adjusted odds ratios.', 'Between 2005 and 2010, 42,919 patients underwent cystectomy. During this period, the prevalence of MIC increased from 0.8% to 10.3% of all cystectomies. Compared with OC, MIC patients were more likely to be male (P\xa0=\xa0.019) and treated at large teaching hospitals (P\xa0<.001). There were no significant differences in age, race, Charlson index, or region between groups. The\xa0median lengths of stay were 8 and 7\xa0days for OC and MIC, respectively (P\xa0<.001). In multivariate regression analyses, MIC was associated with a 30% decreased likelihood of any PSI (odds ratio, 0.71; P\xa0=\xa0.038). Although the occurrence of any PSI was associated with increased mortality (P\xa0<.001), there were no significant differences in mortality between OC and MIC.'] Is minimally invasive cystectomy associated with improved perioperative patient safety outcomes compared with open cystectomy in a national cohort?