Background & Aims: Endoscopist-directed propofol sedation (EDP) remains controversial. We sought to update the safety experience of EDP and estimate the cost of using anesthesia specialists for endoscopic sedation. Methods: We reviewed all published work using EDP. We contacted all endoscopists performing EDP for endoscopy that we were aware of to obtain their safety experience. These complications were available in all patients: endotracheal intubations, permanent neurologic injuries, and death. Results: A total of 646,080 (223,656 published and 422,424 unpublished) EDP cases were identified. Endotracheal intubations, permanent neurologic injuries, and deaths were 11, 0, and 4, respectively. Deaths occurred in 2 patients with pancreatic cancer, a severely handicapped patient with mental retardation, and a patient with severe cardiomyopathy. The overall number of cases requiring mask ventilation was 489 (0.1%) of 569,220 cases with data available. For sites specifying mask ventilation risk by procedure type, 185 (0.1%) of 185,245 patients and 20 (0.01%) of 142,863 patients required mask ventilation during their esophagogastroduodenoscopy or colonoscopy, respectively (P < .001). The estimated cost per life-year saved to substitute anesthesia specialists in these cases, assuming they would have prevented all deaths, was $5.3 million. Conclusions: EDP thus far has a lower mortality rate than that in published data on endoscopist-delivered benzodiazepines and opioids and a comparable rate to that in published data on general anesthesia by anesthesiologists. In the cases described here, use of anesthesia specialists to deliver propofol would have had high costs relative to any potential benefit. © 2009 AGA Institute.