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The aim of the study was to assess, by a review of published evidence, the safest and most effective way to provide procedural sedation (PS) in children undergoing gastrointestinal endoscopy (GIE).The databases MEDLINE, Cochrane Library, and Embase were used. Search terms “endoscopy, gastrointestinal” or “endoscopy, digestive system” were combined with “sedation,” “conscious sedation,” “moderate sedation,” “deep sedation,” and “hypnotics and sedatives.” The final review was restricted to studies reporting specifically on safety (incidences of adverse events) and/or effectiveness (time characteristics, need for supplemental sedation, need for restraint, procedural success, provider satisfaction, and patient comfort) of PS for GIE in children younger than 18 years.The search yielded 182 references and the final selection included 11 randomized controlled trials (RCTs) and 15 non-RCTs. Six sedation categories were identified: propofol, opioid/benzodiazepine, premedication, ketamine-, sevoflurane-, and midazolam-based. Only a few RCTs have compared different categories. Opioid/benzodiazepine- and propofol-based PS have a similar safety profile and a low incidence of major adverse events. Propofol-based sedation turned out to be the most effective regimen, with effectiveness comparable to general anesthesia. The addition of midazolam, fentanyl, remifentanil, and/or ketamine to propofol may increase the effectiveness without creating more adverse events. Data on midazolam-, ketamine- and sevoflurane-based sedation were generally too limited to draw conclusions.Despite a lack of RCTs containing all aspects of effectiveness and safety, the present evidence indicates propofol-based PS to be the best practice for PS in children undergoing GIE. Propofol can be safely administered by specifically trained nonanesthesiologists.