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Are 223 and 5.56 Interchangeable? While similar, the two rounds aren’t the same and shouldn’t be treated as interchangeable. While you can safely fire .223 Remington Ammo from a firearm chambered in 5.56x45 NATO, it doesn’t work both ways. In other words, you shouldn’t fire 5.56 in your rifle if it is chambered for .223. Basically, 5.56 is loaded at higher pressures than .223 and using the 5.56 in a rifle chambered for .223 Remington could lead to a catastrophic failure and serious injury.