Can an 12V 2x4-pin substitute for a 12V 8-pin?

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You can plug both in, it won't hurt anything. It may even help if your power supply is designed as a single rail or even a big double rail unit. Power supplies with multiple rails with have both the 8-pin and 2x4-pin on the same rail, with a limited amount of power available for each rail. So while they both may be plugged in they still can't supply more power than just one connector. But if you have 1 or 2 big rails then there's usually more than enough power on each rail for both connectors.
 
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