Bug report: IrfanView won save settings! Why?
There are 2 possibilities, first: your INI (i_view32.ini) file (or whole IrfanView folder) is set to read-only, please change that; second: some “smart” washer/restore tools/plugins are washing too much, please exclude IrfanView files/folder from such actions. You can also redirect the INI file to another folder (see another question below); also possible during the installation.