Quote Originally Posted by Ignatius881
Hello.

I don't know how many distros I've used with this... Four.

Well, I didn't have problems installing Ubuntu, Debian and openSUSE on an USB hard drive. It was very easy.

But I always want to be sure. Is it possible to install Knoppix on it? I don't want to lose data of my main hard drive (on which I have Windows Vista).
My answer is simple: Don't do it. The easy and safe way to run Knoppix off your USB drive is to prepare a FAT32 partition on it. Then, install Knoppix on that, just like on a USB stick, and prepare persistent storage on the FAT32 partition. That is kind of pseudo-install, where only files are affected, and partitions are not changed.