Background and Purpose— In Germany, all surgical and endovascular procedures on the carotid bifurcation must be documented in a statutory nationwide quality assurance database. We aimed to analyze the association between procedural and perioperative variables and in-hospital stroke or death rates after carotid endarterectomy. Methods— Between 2009 and 2014, overall 142 074 elective carotid endarterectomy procedures for asymptomatic or symptomatic carotid artery stenosis were documented in the database. The primary outcome of this secondary data analysis was in-hospital stroke or death. Major stroke or death, stroke, and death, each until discharge were secondary outcomes. Adjusted relative risks (RRs) were assessed by multivariable multilevel regression analyses. Results— The primary outcome occurred in 1.8% of patients, with a rate of 1.4% in asymptomatic and 2.5% in symptomatic patients, respectively. In the multivariable analysis, lower risks of stroke or death were independently associated with local anesthesia (versus general anesthesia: RR, 0.85; 95% confidence interval [CI], 0.75–0.95), carotid endarterectomy with patch plasty compared with primary closure (RR, 0.71; 95% CI, 0.52–0.97), intraoperative completion studies by duplex ultrasound (RR, 0.74; 95% CI, 0.63–0.88) or angiography (RR, 0.80; 95% CI, 0.71–0.90), and perioperative antiplatelet medication (RR, 0.83; 95% CI, 0.71–0.97). No shunting and a short cross-clamp time were also associated with lower risks; however, these are suspected to be confounded. Conclusions— Local anesthesia, patch plasty compared with primary closure, intraoperative completion studies by duplex ultrasound or angiography, and perioperative antiplatelet medication were independently associated with lower in-hospital stroke or death rates after carotid endarterectomy.