Hi Dan

This is a first. I've only got single domains to test against and I've never had anyone ask or mention the problem you're having. My initial reaction is that it should work as the usernames  are different when they get entered into the db seeing as they go in as DomA\JSmith and DomB\JSmith. That said, I'd have to step through the code to see where it's going sideways. Because I don't have multiple domains to work with that's impossible for me to do at the moment.

Found it...kind of. When the domain name(s) are entered in uppercase it works. 

I see a ToUpper in the code for handling the domain part of username@dom logins but not for handling the domain part of dom\username logins.
 I have yet to succeeded in fixing the code itself on my site(s).

Since AD Domain names are not case sensitive, I'm not sure why it matters, but it apparently ADSI expectes capitaliation does someplace deeper in the code.

Message:
System.NullReferenceException: Object reference not set to an instance of an object. at DotNetNuke.Authentication.ActiveDirectory.ADSI.Utilities.AddADSIPath(String Path, Path ADSIPath) at DotNetNuke.Authentication.ActiveDirectory.ADSI.Utilities.GetDomainByBIOSName(String Name) at DotNetNuke.Authentication.ActiveDirectory.ADSI.Utilities.GetUserEntryByName(String Name) at DotNetNuke.Authentication.ActiveDirectory.ADSI.ADSIProvider.GetUser(String LoggedOnUserName, String LoggedOnPassword)