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Yes it should run HDX just fine. I have a 10th Gen. i9 10850K with a Gigabyte Z490 Vision D mobo and all is well. When building your system make sure you install Windows and get it running first before you install your HDX card (UAD2). If your using the internal graphics card you should be able to get the BOIS to post (viewable) immediately. When using a GPU card I had to re-seat it a few times before the BOIS would post (I can tell someone what I did if they run into any problems). You need to use a GPU card cause several plugins I use would not open (UI wasn't visible) when I used the internal graphics card so I had to use my GPU (You may or may not run into this problem). The HDX card for my build had to go in the 2nd PCIe slot or it wouldn't work if I remember correctly. I forget what slot my UAD2 card is in. I have my M.2 drive in the first M.2 slot so it's running off my CPU and not taking any of my six SATA lanes. All my UBS3 and USB2 ports are working fine. I'm not using the Thunderbolt 3 ports but I hear they work fine. Once you get everything running smoothly, please clone your system drive with Acronis or Macrium Reflect, Please do this ASAP. This will save you alot of frustration if your system starts acting funny or an Windows update breaks something. You can thank me later.