Once you have set up multiple profiles, either for an installed or portable Thunderbird, you can use them one at at time (the default), or run them concurrently.
Use the above links to learn about using the switches
-no-remote(installed)AllowMultipleInstances=true(portable)
These switches allow multiple profiles, multiple thunderbirds, and even different thunderbird releases, to run simultaneously. You can even run portable and installed versions side by side. Every profile loaded must use -no-remote or AllowMultipleInstances=true as applicable.
🔹 Example
Here is a sample <username>\AppData\Roaming\Thunderbird\profiles.ini and it's matching Profile Manager
[General]
StartWithLastProfile=1
[Profile0]
Name=hardened
IsRelative=0
Path=D:\UserData\Thunderbird\Profiles\hardened
[Profile1]
Name=relaxed
IsRelative=0
Path=D:\UserData\Thunderbird\Profiles\relaxed
Here are four corresponding shortcuts
"C:\Program Files\Mozilla Thunderbird\thunderbird.exe" -no-remote -p "hardened"
"C:\Program Files\Mozilla Thunderbird\thunderbird.exe" -no-remote -p "relaxed"
"C:\Program Files\Mozilla Thunderbird\thunderbird.exe" -p
And here are all three profiles running concurrently, with both normal and private browsing mode windows. To help distinguish each profile visually, it is recommended to assign each one a theme.
🔹 Caveats
When running profiles with AllowMultipleInstances=true (portable), external commands (such as clicking links in emails, double-clicking URL shortcuts, etc) will fail. Even profiles with -no-remote (installed) may fail - it depends on your system and the default browser registration.
Note: you can still drag and drop shortcuts and paste links, you just can't use system integration to launch from an external application.