I've seen a calibre library with well over 250,000 books. In theory, the SQLite database used to store the library information could handle up to 2,147,483,646 entries though that could result in a 140TB database.
As to why you are having books disappear, you might want to check in the calibre forum. That was a known issue where file/directory locking prevented calibre from removing a book when, for instance, the author name was changed. A search for 'file locking' in the calibre forum will come up with more information. A couple of threads that might be helpful are
Calibre deleting files after edit metadata and
Books missing from library but showing metadata?.