In our database we hawe 2 file formats of .iss file extension. If you have a problem with using .iss file extension – we can help You. Below is a list of programs that support the file type of InstallShield Silent Response File for all operating systems. If at any time in the future you will have a problem with any file extension, please visit our File Extensions Database. From today, the question - How to open file .iss - There won't be a problem.