XLS Views 8 meanings found XLS is widely recognized as the file extension for Microsoft Excel spreadsheets, but the same letters also identify an excimer laser system in medicine and a xenon light source in scientific research. Medical Excimer Laser System Academic & Science Extended Light Scatterer Xenon Light Source Regional St. Louis, Senegal Computing Microsoft Excel Spreadsheet Microsoft Works Spreadsheet Business Xtra Long Stroke Exelis Inc.