I have the same problem. I exchanged the first remote and watched the second one carefully as I set it up. I noticed that after the first successful sync, the MyHarmony software downloads and installs a firmware update. This is where the syncing problems start.

I have tried both USB 3 and USB 2 ports. Windows sees that the remote is connected. Even the remote's screen shows it connected.

The mostly useless Logitech "support" claims that if the MyHarmony software manages to see the remote, starts a sync and gets to 99%, then you are good to go. This is also not true. More often than not the changes are not recorded.

I have called, emailed, posted on their Facebook page and even called and emailed their "Manager of Harmony Support" but once you prove to Logitech support that their software and/or remote is broken they run away and stop responding. You can look at reviews on Amazon.com and other sites and you'll see many users with the same problems.

After making these remotes and software for so many years you'd think Logitech would have their act together.