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I installed a game and it works through PlayOnLinux.  But the issue comes whenever I want to launch the game a second time.  When I try to launch the game from the created icon, PlayOnLinux will double launch the game, and when I exit the game the second launched game will resize the screen, make any attempts to close it or interact with anything on the screen impossible (the mouse can still move and I can still launch the menu, but I can't interact with anything), and then a hard reboot of the computer is required.

I have no clue why PlayOn will only allow the game to work on a fresh install, but that's how it is.  Having to delete the virtual drive, create a new one, and create a new install every time I want to play the game is very, very annoying.  I just want to be able to play the game more than once without killing the computer.

This is very common with a lot of games in PlayOnLinux.  I've learned that after closing a game to check the activity monitor and if there are Windows executables still running, then the game has not officially closed or exited.

So I go to Configure -> Wine Tab -> Kill All Processes

That will kill all the executables so you can run it again without multiple copies running which cause memory issues.

Let me know if this helps!

Forth, please give some details about OS and version, POL version, game name.