We had a major issue with Adobe Acrobat where each and every file the user tried to save resulted in the error message
The document could not be saved. The file may be read-only, or another user may have it open.
The only method was to save the file to the desktop and then copy it back to the original folder which worked just fine.
After a lot of searching and trying out a lot of things (including accusing our AV software, as always) where were finally to resolve this by accident.
The reason for this message is the preview pane of Windows 7! If you have it open, Acrobat will lock the file so Acrobat can’t change it. When the user double clicks the file it is automatically selected, triggering the preview and the file is locked.
Turn off the preview window in Explorer and everything will work.