Hi Henrik, thank you for the response. That Rescan button doesn’t fix my situation. But i was able to find a solution, posting it here for posterity.

Original issue:
1. SD3 is running, my Roland TD50 is connected. All is well.
2. Turn off the Roland TD50 module, leave SD3 running. As expected, SD3 is disconnected from module.
3. Turn TD50 back on. Switch back to running instance of SD3. Module is still disconnected.
4. From SD3 menu | Settings | Audio Midi Setup | Rescan devices. After this, module is still disconnected.
5. The original solution was to turn off / turn back on SD3. The connection between SD3 and TD50 would be re-established.

I found a simpler solution:
I was routing audio from my Mac back into the TD50, so that i could use the headphone jacks on the roland module. When the module is power cycled (off, back on), the connection *can* be re-established by resetting the Audio Device (Settings | Audio Midi Setup | Audio Device) back to TD50. TO do this select TD50 and hit apply. Not sure if this is a software glitch, but it’s much less painful than restarting SD3 each time.

I still have a gripe about the ‘Save Project’ dialog that pops up constantly. Seems that it should be smart enough to know to not prompt if the file has not been modified. For example, if you configure everything and then use SD3 | File | Save as Default. Start and restart SD3. It immediately asks if you want to save the project before loading the defaults. Super strange!