Hi. New here and have reviewed open topics quickly but no joy.
I have ThunderbirdPortable working nicely on both GMail and another (Shaw) webmail account, loaded on a large capacity brandname USB thumb/flash drive.
After finishing my email work, and Closing/Exiting TBP, I cannot safely eject my USB drive ('busy', close open apps, etc.).
If I am working in the PortableApps alone (including installs/updates to apps) without opening and closing TBP, I can safely eject my USB drive ('safe to eject hardware').
This occurs both on my managed workstation Windows 7 and on my home laptop Windows 8.1, on any USB port (pretty sure the workstation is at a glorious 1.1, my laptop has both 2.0 and 3.0 ports).
I have searched the web extensively and am at a loss, seems to be only me (or I'm not using the right search terms). 
Any suggestions?
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If you check Task Manager, is either thunderbird.exe or ThunderbirdPortable.exe still running? Are you running any extensions?
Sometimes, the impossible can become possible, if you're awesome!
Nothing in Task Manager (checked right away with the message "drive busy....apps still running" on either box.
Running the installed the TBP just as it comes (i.e., no extensions/add ons to my knowledge).
PS: SanDisk Cruzer w Security (not using the Secured folders/Security) 128gB and only been using PortableApps on it for a few weeks (rescued everything from a previous drive of 32gB starting to have disk errors).
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Jude
Try one of the unlocker utilities from our Utilities section to determine what process or file is locking something on the drive. Sometimes antivirus or other apps on the PC can lock things on a flash drive. This can happen more often with an email client as some antivirus detects running email clients and automatically scans emails, locking Thunderbird's mail files.
Sometimes, the impossible can become possible, if you're awesome!