I did some testing.
I am running Windows 10 Pro Creators Version. (64-bit system). I am running the game on Origin. (This might help you guys on Steam too. Just try it and let me know or just comment.)
I ran a shortcut the #2 trainer in Windows 7 Compatibility Mode as an Administrator.
If you dont know how to do that. Right click on the Shortcut. Go to properties. Then the compatibility tab. The first option with a check box is the which version of Windows to run it in. Select Windows 7 in the drop down. (So check the "Run this program in compatibility mode for:" Then select Windows 7 in the drop down.
Its usually the best option for games older than 3-4 years old and you are having problems with the game or the trainer running. Some games just cant handle Windows 10 (and heaven forbid you have Windows 8.)
The last option in the Compatibility tab is Run this program as administrator. Make sure that is checked.
That should work if you are having issues with Windows 10. Also, make sure you follow the directions in, the venerable, Mr. Antifun's first post. Do not open this until you are loaded into the game and can play it. Don't open it when you are in the first menu. Only after you load in and move Isaac (your character around).
The TLDR: Run a shortcut of the trainer in Compatibility for Win7 and with Run this program as administrator. Only open/run the trainer once completely in the game.
Edited for this: Its always safe to try Windows 7 compatibility when having issues. Especially with older games.
