Background: Postinterventional sedation is commonly used in clinical practice to ensure patient safety and comfort. Although sedation or anesthesia during thrombectomy has been well studied, the association between postinterventional sedation and functional outcomes in endovascularly treated patients with acute ischemic stroke (AIS) has yet to be investigated. We describe the association between postinterventional sedation and functional outcomes in patients with AIS treated with endovascular therapy (EVT). Methods: This observational study was based on a prospective registry. Patients with AIS treated with EVT from January 2013 to August 2017 at Xuanwu Hospital, Capital Medical University were included. Patients receiving postinterventional sedation were compared with patients not receiving sedation. The primary outcome was the 3 months modified Rankin Scale score. Results: A total of 268 patients were eligible for study: 112 patients (41.8%) receiving postinterventional sedation and 156 patients (58.2%) without sedation. At 3 months follow-up, the median modified Rankin Scale score was 4 (interquartile range, 3–6) in the sedation group and 2 (interquartile range, 1–4) in the nonsedation group (P < 0.001). Multivariable regression analysis suggested that the need for postinterventional sedation was associated with unfavorable outcomes, with an odds ratio of 0.20 for functional independence (95% confidence interval [CI], 0.078–0.487; P < 0.001), 0.06 for freedom from disability (95% CI, 0.017–0.228; P < 0.001), and 8.37 for death (95% CI, 2.196–31.889; P = 0.002). Conclusions: Postinterventional sedation worsens functional outcomes in patients with AIS with large-vessel occlusions treated with EVT. Whether the sedation is a causative factor or a surrogate for poor functional outcomes remains to be determined. © 2019 Elsevier Inc.