The use of sedation with peroral passage of conventionally sized endoscopes for upper endoscopy is the standard practice for most endoscopists in the United States. The administration of sedatives requires time-consuming and resource-intensive patient monitoring, has substantial cost, and can produce side effects and rare complications. Ultra-thin videoendoscopes (outer diameter less than 6 mm) have been developed, can easily be passed transorally or transnasally without sedation, and have been shown to be well tolerated and accurate. Unsedated upper endoscopy can provide an efficient, cost-effective alternative to standard endoscopy, should be useful for endoscopic screening, and can be offered as an option to conventional sedated examination.