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This generally happens when the game does not have proper permissions or space to save to the hard drive.
There are several potential reasons for this.
Probably the most likely is that you have an anti-virus or disk cleaner type of program that has either deleted some game files or is blocking the game when it tries to save. So to fix this, be sure to set an exception (whitelist) in your anti-virus programs for both the ootp21.exe and for any OOTP related folders, especially the folder OOTP uses for saving games.
Another potential source of the problem is not having proper write permissions for the game. The main fix for this would be to run the game in admin mode. Also, check the OOTP saves folder and make sure that is not read only or somehow write protected.
A third potential source of the problem is not having enough space on the hard drive you're trying to save to. Even if you think you have enough space, check to make sure OOTP is not saving to a smaller partitioned area of a hard drive that might be out of space (for instance, if you have your OS installed on a small partition, make sure OOTP didn't somehow get set to save to a folder on the partition, not your regular drive).
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