The method for sending different users' mail using multiple Mail Senders in VPOP3 works well for up to 10 ISP relay accounts, but cannot be used for more than that, and can become cumbersome before that.

The method listed below requires VPOP3 7.0 or later, but may be easier to use if you have many ISP relay accounts. Note that it is still probably easier to use an SMTP relay service which allows you to send all your mail through a single account, but that may not be possible for you for some reason.

This method requires you to configure your Mail Sender in VPOP3 to use 'MX Sending'. This method usually sends mail directly to the recipients' mail servers, without going through your ISP, and is normally only recommended if you have a leased line or your VPOP3 server is hosted in a data centre because recipients will often block mail from ADSL/Cable connections. However, the method shown in this article 'tricks' VPOP3 into sending via your ISP's relay servers instead of directly to the recipient.

Set the Mail Sender to use 'SMTP Direct' sending