Windows.old isn't only created when reinstalling or upgrading to a new version Windows, but also during major Windows updates.
What is stored in the folder? Only system files or user data as well? I have lost Nvidia Control Panel settings in Windows 10 Anniversary Update and again in the recent Windows 10 Creators Update, but otherwise I haven't observed any loss of personal program data.
Is deleting with the Disk Cleanup tool safe, as long as I'm not reverting to an earlier version of Windows and I'm willing to reinstall in the case of major issues?