Try exiting out of the Steam client, if applicable, and starting the game directly from the '..\SteamApps\common\Divinity Original Sin 2\DefEd\bin\EoCApp.exe' program file, by right clicking and running as administrator (or '..\Divinity Original Sin 2\Classic\EoCApp.exe' for the original release).
Try right clicking the game executable, select Properties, switch to the Compatibility tab and check off the 'Override high DPI scaling behavior' option (set it to Application), maybe run as administrator, and set a Win 7 or 8 compatibility mode. That fixed this error for one person in Win 10 (the OP specified that they had to set Win 7 compatibility and disable fullscreen optimization).
Check for updated graphics drivers; that help one person getting this error. If you already have the latest, and other troubleshooting doesn't help, you can try a clean re-install of the graphics drivers; see
here or
here, for example.
If applicable, disable Steam cloud support either globally (in the client click on the Steam menu and select Settings, and then Cloud) or just for this game (in the library right click Divinity: Original Sin 2 and select Properties, then switch to the Updates tab and check the Steam Cloud section).
Alternately, exit out of the Steam client, or Galaxy for the GOG version, and just start the game directly from the executable when required.
Next, try browsing to the '..\Documents\Larian Studios' folder and rename the 'Divinity Original Sin 2 Definitive Edition' subfolder.
This folder contains the saved games, configuration files and a level cache folder. Deleting or renaming it will get the game to recreate it on startup; playing the game from a different Windows user account would effectively do the same thing. With Steam running and cloud support enabled, the client would just download the cloud copy of your existing profile, if applicable.
After that, extract the replacement folder from
this download into your '..\Documents\Larian Studios' folder, and see if that will let you start the game.
The graphicSettings.lsx file is set to 1280x720 Windowed mode, Very Low quality preset and low audio quality, which you can change in the options (manually, or hit autodetect) if this gets the game to start.
If that helps, try increasing the resolution and switching to fake fullscreen, then see if you can exit and restart. If so, try again for fullscreen. If that helps (it did for one person online, with a different game), move your original profile folder back (or create a new profile, exit and move the saves over to the newly created profile's ..\Savegames\Story folder).
If you continue to get the same error, delete the replacement My Documents D:OS 2 DE folder and rename the original back again.
Try checking your system files:
- click Start, type cmd into the search box, right click Command Prompt and select run as administrator.
- type the following command and hit Enter
sfc /scannow
When that is done, type exit and hit Enter, then reboot your computer.
For more details, see:
https://support.microsoft.com/en-ca/kb/929833Try doing a clean boot and then test the game. Click Start, or hit WinKey-R, type in msconfig and hit enter; in the General tab, click Selective Startup, uncheck Load startup items (if required) and leave Load system services and Use original boot configuration options checked. Next, click on the Services tab, check the box to Hide all Microsoft services, then click the Disable All button (maybe make a note of which are currently enabled/disabled), then click OK and reboot the computer.
Run msconfig again to switch back to the normal boot configuration.
Try creating a new Windows administrator user account, switch to that account and try starting the game from there, directly from the executable.
