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Ambulatory procedural sedation is used to relieve anxiety, pain and discomfort in a broad spectrum of patients during many types of diagnostic or therapeutic procedures. This review focuses on recent comparative studies of commonly used and new drugs for adult ambulatory sedation.Midazolam and propofol are commonly used for ambulatory sedation. Their pharmacological properties offer many advantages and there is much experience with their use. Ketamine can be a useful addition to hypnotic drugs but the advantage of the use of ketofol (a mixture of propofol and ketamine) is, although often practiced, difficult to assess. Dexmedetomidine is a relatively new sedative drug and many studies suggest advantages. New findings about its effects, however, show that the hemodynamic consequences of the use of dexmedetomidine may last for several hours. New sedative drugs for procedural sedation are still being developed: remimazolam has many properties that would make it an ideal sedative and has been studied in a phase 3 study.The properties that would constitute the ideal sedative have yet to be combined in one drug. The selection of the drugs used for ambulatory sedation depends on many factors such as procedure type, patient characteristics and the expectations of patients and the healthcare provider. Because of this, the literature cannot yet provide a definitive answer to the question which drug is best selected in a specific situation.