In South Korea, as in many other countries, propofol sedation is performed by practitioners across a broad range of specialties in our country. However, this has led to significant variation in propofol sedation practices, as shown in a series of reports by the Korean Society of Anesthesiologists (KSA). This has led the KSA to develop a set of evidence-based practical guidelines for propofol sedation by non-anesthesiologists. Here, we provide a set of recommendations for propofol sedation, with the aim of ensuring patient safety in a variety of clinical settings. The subjects of the guidelines are patients aged ≥ 18 years who were receiving diagnostic or therapeutic procedures under propofol sedation in a variety of hospital classes. The committee developed the guidelines via a de novo method, using key questions created across 10 sub-themes for data collection as well as evidence from the literature. In addition, meta-analyses were performed for three key questions. Recommendations were made based on the available evidence, and graded according to the modified Grading of Recommendations Assessment, Development and Evaluation system. Draft guidelines were scrutinized and discussed by advisory panels, and agreement was achieved via the Delphi consensus process. The guidelines contain 33 recommendations that have been endorsed by the KSA Executive Committee. These guidelines are not a legal standard of care and are not absolute requirements; rather they are recommendations that may be adopted, modified, or rejected according to clinical considerations.