If you are unable to defragment your hard disk normally due to an
application that is running in the background, you will succeed in Safe
Mode, where applications that normally start with Windows do not run.
However, it's just as easy if not easier to temporarily suspend whatever
application is interfering.
Safe mode may have helped for Win98 where the defragger would restar
itself at the slightest provocation but in Win XP, I've found tha
there are hardly any files that are exclusively defragmentable in saf
mode. Atleast from my casual observations.
With commercial defraggers like Diskeeper, you definitely do not nee
to use safe mode. I am running Diskeeper 2009 Pro on a XP system and i
completely defrags the drive when you use it with the automatic defra
option within the Windows 'normal' mode. It defrags even the MFT thi
way without any additional step