Hi, I promise I won't ask "Why would You want to do something like that?!".
First thing You should remember is that the hard drive is still the same physical hard drive used in an internal situation, it's just using an added case that can plug into a different connector on the computer. This means that it follows the same rules as an internal hard drive.
The situation You're describing to the Why askers above sounds like what I started doing a few years ago - whenever I buy new external drives now (usually about 1tb for $60) I add a 32Gb primary partition and "Live install" a couple of linux OS'es to it, then create the rest of the drive as an extended partition and format it to NTFS, which can also be used on a Windows system.
The main thing to remember when re-partitioning an older hard drive of any kind is that whatever Windows You used to partition it with the first time decided what types of partitions it can and will have - That's important because older Windows versions only supported the most recent types when they were released - so Windows XP doesn;t support some formats that Windows 7 does, or that Windows 2000 did, etc ...
If You want to guarantee that the drive can be used on most modern systems, You should copy the data from it temporarily, wipe the current partitions completely, and re-create new pratitions with something as current as a free version of Puppy linux from a flashdrive or CD. It can use the most recent formats & partitioning methods up to about 6 months ago, which means it will also support compatibility with drives as large as 4+ terabytes. And the read/write speeds will also see an improvement because of the larger block sizing and newer file-handling & RAM-Swap methods.
G'Luck!!.