If it's a USB 1.1 drive, then yes....is there a noticeable degradation of performance as compared with booting from an internal drive?
If it's a USB 2.0 drive, then not much.
If it's a FireWire 400 drive, then even less so.
If it's a FireWire 800 drive, probably not at all.
If it's an eSATA drive, you probably couldn't even tell.
Is there some reason you need to boot from an external media instead of the internal drive?