IMO its best run Defrag in safe mode, it will run slower with any other applications running, and MAY affect the end results as it cannot access all the files because they might be being used. -Pepsi

Defragmentation starts from the begining if some program from the drive being defragmented is run.

1) It is okay starting with Windows Vista. And yes, it could make the defragmentation go slower. The end result should be the same. But an application with low resource needs would not be a problem. If you are surfing on the web, it would be OK as long as you are not watching videos, for instance. With older Windows versions, the defragmenting would stop and always restart if you were doing something at the same time. So you could not use it that way. 2) "Windows Disk Defragmenter is a computer program included in Microsoft Windows designed to increase access speed (and sometimes increase the amount of usable space) by rearranging files stored on a disk to occupy contiguous storage locations, or defragmenting. The purpose is to optimize the time it takes to read and write files to/from the disk by minimizing head travel time and maximizing the transfer rate." "In Windows Vista, Windows Disk Defragmenter includes an option to automatically run at scheduled times and uses low CPU priority and the newly introduced low priority I/O algorithm so that disk defragmenter can continue to defrag using reduced resources (less CPU and disk read/write activity) when the computer is in use. The user interface has been simplified, with the color graph and progress indicator being removed entirely. It is also currently not possible to select which drives to defragment (though the feature will be included in Service Pack 1 of Windows Vista). Chunks of data over 64MB in size are not defragmented; Microsoft has stated that this is because there is no discernible performance benefit in doing so. The result, however, is that Disk Defragmenter does not require a certain amount of free space in order to successfully defrag a volume, unlike previous versions which required at least 15% free space on the volume. The command line utility, defrag.exe in Windows Vista, offers more control over the defragmentation process. This utility can be used to defragment specific volumes or to just analyze volumes as the defragmenter would in Windows XP." Source and further information: http://en.wikipedia.org/wiki/Disk_Defragmenter_(Windows)

yes of course it will run slow and it will definately effect ur pc if ur running another application. never run any application if ur running a system scan like antivirus or disk cleanup/defragmentor etc. let the scan finish and then run any other application.