vSphere 6.5 – Transport (VMDB) error -45: Failed to connect to peer process

While upgrading some Cisco UCS B200 M3 Servers from vSphere 6.0 to 6.5, I ran into an error that I could not figure out. After upgrading the first Cisco Blade to 6.5, I could not vMotion any VMs from the older 6.0 host to the newly upgraded 6.5 host. I would get the following error:

Transport (VMDB) error -45: Failed to connect to peer process

I was able to vMotion a powered off VM to the new host, but when I attempted to power on the VM, I got the same error: Transport (VMDB) error -45: Failed to connect to peer process

After poking around for awhile, I decided to turn to the VMware community, where I most mostly seeing this error with people using Workstation and Fusion products, but there wasn’t much going on with ESXi environments. I made sure to use the ESXi 6.5 Cisco Media for the original installs and this upgrade, and I assumed there had to be a driver/component issue with all of this. I tried updating by booting into the ISO and running the upgrade from there. After attempting to manually upgrade drivers and firmware, the solution that worked for me was the following:

Reinstall the freaking host from scratch! 

There you have it. Such a simple solution 🙂
Honestly, I have no idea why the reinstall was necessary. I ran into the same issue again when trying to upgrade that second host, and I even tried upgrading it using the an alternative method (Using ESXCLI and Update Manager), but no luck.

I did not call VMware Support on this, but I did submit the bug report. I would love to hear from someone who figured out the root cause and workaround.