The very first time you start EndNote, you will probably get a "splash" screen. Click on it to close it.
Closing the splash screen will give you the New Library screen.
From the File menu, select New or alternatively, click the Create a new library button. Give your file a name and save it.
This will give you a new empty references database that EndNote calls a "library".
Choose a location on your hard disk that you are unlikely to change (e.g. in the Documents folder, possibly in a subfolder e.g. create a subfolder for Research).
Do NOT use folders synced or proxied with online systems (e.g. do NOT use Dropbox, Google Drive, OneDrive, iCloud, etc, as the working folder for your EndNote library).
(The default name of "My EndNote Library" is fine, but this is the default name for any new library, so renaming it to something like MyResearch or MyThesis is both more unique and decreases the chances of it being overwritten if you create a new library.)
There are 5 main areas that you will be working with:
