When is the macro TARGET_OS_SIMULATOR used? Can it be used as an replacement for TARGET_IPHONE_SIMULATOR to check at runtime if app is running on simulator or device?

… to check at runtime if app is running on simulator or device?

This part of your question makes no sense. An app can't be built so that the same binary runs on the simulator and runs on the device, so it makes no sense to do a runtime check to see whether you're on the simulator or the device. Such a check would always be at compile time.

However, to answer your question about the difference between

TARGET_OS_SIMULATOR

TARGET_IPHONE_SIMULATOR

<TargetConditionals.h>

TARGET_IPHONE_SIMULATOR   - DEPRECATED: Same as TARGET_OS_SIMULATOR

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