It depends on the program. Most commercial programs rely on the registry to operate and/or store settings (which resides on the system partition), so won't work, or will have problems, if the registry is changed. Some other programs install various files on the system partition no matter where you install them (like drivers, codecs, etc) and so won't work at all with a renewed operating system install. If you backup the registry before you format/reinstall the OS partition, you should be covered for most programs.
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