The safest way to defrag your disk is to not defrag. Especially large files.
SO what to do?
First thing to remember is to never have all files on 1 partition. If you have a 300 gig HD, break it into 100 and 200 gig. If you want to defrag the 100 gigs, move all the files to the 200 partition and format the 100 gig side, then move it all back. This will create a new format table and will place the files in an efficient order.
NOTE: you cannot do this with your operating system partition or partition that contains program files. I am talking about storage drives mainly.
As for the 200 gig side, you can also have an external hard drive, transfer to that drive and then format the 200 gig side.
This advice is coming from a 10 year Computer Service Engineer. If you only knew how many hard drives I have seen fail due to defraging. I personally rarely do it, I would rather deal with the micro seconds slower data transfer times. Has anyone ever really noticed a performance boost after defrag? Or is the fact that our files are all jumbled and disorganized drive us humans crazy?
Defraging your operating system and program files drive is fairly safer, in my opinion.