open Explorer window
This will frequently be the problem, but something else is also going on. I use two USB hard drives, both plugged in at the same time. Closing Explorer will always free up my 500GB, but almost never my 2TB - in fact I nearly always have to reboot to clear the larger drive, because it remains "in use" even with *all* windows closed other than the desktop. And there's nothing on the desktop requesting it.