Generally you will only need one EndNote Library, as it can hold a vast amount of references (999,999). You can then divide up your references for various tasks, or for various threads of your research, using Groups and Group Sets (see Using Groups and Tags for more information).
If you want to have more than one EndNote Library we recommend that you not use more than one library with the same Word document, as this can become confusing and cause errors.
There are two main ways of backing up your EndNote library:
Set up a free EndNote Web account to create an online backup of your library (see EndNote Web and Sharing Libraries link below for more information)
You can then access your EndNote library on different computers (or on EndNote's iPad app) by syncing with EndNote Web. This method has the advantage that the backup is always up to date; but the disadvantage of needing to be connected to the internet to use it. Syncing can also take a while.
Create a Compressed Library (.enlx) as your backup, and store it on a different drive from your main EndNote library.
Compressed libraries can be created in EndNote using File > Compressed Library. A compressed library contains both the EndNote library (.enl) file and its accompanying data folder in a single file.
You can then store the compressed library on a detachable device such as a USB, and continue to use the original EndNote library on your computer.
Alternately, you can store the compressed library on your computer, and keep the original EndNote library (with its .Data folder) on a detachable device. This would be a good system if you needed to be able to open your EndNote library on several different computers.