Context. Observer-based sedation scales have been used to provide a measurable estimate of the comfort of nonalert patients in palliative sedation. However, their usefulness and appropriateness in this setting has not been demonstrated. Objectives. To study the reliability and validity of observer-based sedation scales in palliative sedation. Methods. A prospective evaluation of 54 patients under intermittent or continuous sedation with four sedation scales was performed by 52 nurses. Included scales were the Minnesota Sedation Assessment Tool (MSAT), Richmond Agitation-Sedation Scale (RASS), Vancouver Interaction and Calmness Scale (VICS), and a sedation score proposed in the Guideline for Palliative Sedation of the Royal Dutch Medical Association (KNMG). Inter-rater reliability was tested with the intraclass correlation coefficient Results. Overall moderate to high inter-rater reliability was found for the VICS interaction subscale (ICC = 0.85), RASS (ICC = 0.73), and KNMG (ICC = 0.71). The largest correlation between scales was found for the RASS and KNMG (rho = 0.836). All scales showed discriminative and evaluative validity, except for the MSAT motor subscale and VICS calmness subscale. Finally, the RASS was less time consuming, clearer, and easier to use than the MSAT and VICS. Conclusion. The RASS and KNMG scales stand as the most reliable and valid among the evaluated scales. In addition, the RASS was less time consuming, clearer, and easier to use than the MSAT and VICS. Further research is needed to evaluate the impact of the scales on better symptom control and patient comfort. J Pain Symptom Manage 2012; 44: 704-714. (C) 2012 U. S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.