Zotero allows you to create multiple profiles, each with its own settings and associated data directory. If you're familiar with using multiple profiles in Firefox, Zotero works the same way and supports the same command-line flags.

A default profile is created when you first start Zotero. To create an additional profile, start Zotero from the command line and pass the -P flag to open the Profile Manager:

• Open Terminal via Spotlight or /Applications/Utilities.
• Paste /Applications/Zotero.app/Contents/MacOS/zotero -P into the Terminal window.
• Press Return

• Open the Run dialog (Search/Cortana → type “Run” → Run (Windows 10) or Start → Run (Windows 7)
• Paste C:\Program Files (x86)\Zotero\zotero.exe -P
• Press Enter

• Start Zotero via the command line, adding the -P command-line flag.

If you have your Zotero data directory in the default location (“Zotero” within your home directory), the new profile will use that directory by default when you first start it. Create a new directory — e.g., “Zotero Work” in your home directory — and, in the new profile, point Zotero to that one from the Advanced → Files and Folders pane of the preferences.

You can open a specific profile from the command line with the -p flag (e.g., -p Work), which may be useful for creating shortcuts that automatically open a given profile. (On a Mac, you can save an AppleScript with command-line flags embedded as an application in Script Editor.)

Additional configuration may be required when running multiple instances of Zotero at a time.