I usually leave the Pico-8 application running on my home PC overnight and during the day while I'm at work. If it's in fullscreen, it will silently crash (stop responding) if left open for long periods of time. Interestingly, it doesn't happen in windowed mode (although I haven't tested it with resizing the window to a custom size). The application at that point needs to be closed completely and reopened (good thing I save my work frequently). There is no error shown either in the program, or by Windows (Windows does not report it as "Not Responding" - Pico simply becomes unresponsive to any keyboard/mouse input). I haven't tried looking in Task Manager to see if it's leaking memory or CPU cycles.

• Windows 10 Pro
• AMD FX-8350
• 16GB DDR3
• nVidia GTX 660 (in case it's a display error with nVidia drivers, since for some reason it's caused by window size)
• Installed on a 256GB Samsung EVO SSD
• PC is not set to ever sleep or hibernate, so it's not happening upon "waking up"
• No USB suspend settings are applied that could sever communications between Pico and input devices
• Hard drives and processor are not set to change performance settings while idle
• All power-saving options are disabled
• No screensaver

Funny, I'm having the same problem. In my case, it just crashes the moment I leave fullscreen mode and windows forces me to close it directly.

I see we do have quite a few similarities. I also use Windows 10, and I also installed it on a 256 Samsung EVO SSD. Same configurations. My graphics card, however, is a GeForce GTX 760. My bet is on Windows, though...