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Endoscopic submucosal dissection of gastrointestinal lesions on an outpatient basis. Background: Endoscopic submucosal dissection (ESD) is usually associated with hospital admission. Objectives: To evaluate, prospectively, the feasibility, safety and efficacy of outpatient gastrointestinal ESD. Methods: Patients with suitable lesions were invited to participate. Those that dwelt more than 1 hour from the hospital, lived alone, had severe co-morbidities, were <18 years old, had duodenal lesions, or that had ESD-related complications were admitted. The remaining patients were discharged if no complications were detected. A patients' inquiry was performed. Results: Of the 164 ESD patients, 122 were outpatient-based, corresponding to 115 patients, 47% male and mean age 63 ± 12 years-old. Outpatients tended to be younger, female, to have gastric lesions, less advanced lesions, and shorter and less complicated ESDs (all p < 0.05). Outpatients' mean tumour size was 38 mm, en bloc and R0 resection rates were 88 and 78%, respectively. Seven ESD outpatients (5.7%) had complications: delayed bleeding (n = 4), pneumonitis (n = 2) or emphysema (n = 1), all managed conservatively. Colorectal location of the lesions was predictive of hospital admission (p = 0.03). In total, 97% of patients were satisfied with the outpatient strategy. Conclusion: Risks of ambulatory ESD are low and complications can be successfully managed. This strategy has high patient satisfaction. More studies are needed to evaluate its implications on costs and patients' management.