The most popular rifle in the U.S., the AR-15, is most commonly chambered in 5.56 NATO, but you’ll hear many people refer to it as .223 Rem. This causes a lot of confusion, as the two cartridges are extremely similar, although not quite interchangeable. They fire the same caliber projectile, and the cartridges’ external dimensions are identical. But it’s what’s inside the case and inside the guns themselves that makes the difference.
The short answer is that you can shoot .223 Rem. ammo out of a gun chambered for 5.56 NATO, but you cannot safely shoot 5.56 ammo out of a gun that’s only marked for .223. How bad is it to mix the two up? One way is no big deal; the other is a safety hazard. Why?
There are two main differences between the cartridges. The first is that the 5.56 has a bit more powder and thus a slightly higher pressure level than the .223—about 58,000 psi vs 55,000 psi. Not huge, but it matters.
The second difference is that rifles chambered for 5.56 have a slightly longer “throat,” and 5.56 ammo is designed to work with that length. When you fire a 5.56 cartridge out of a .223 rifle with a slightly shorter throat (the part of the chamber that’s in front of the case), it generates pressure of 65,000 psi or more. The .223 gun is just not designed for that amount of pressure, and it can cause everything from reliability problems to blown primers to damage to the firearm and the shooter.
Conversely, shooting a .223 cartridge out of a 5.56 rifle is safe, but because of that difference in throat length, you might not achieve the velocity and performance/accuracy you’re looking for. It might not even properly cycle the action of a semi-automatic 5.56 rifle, particularly with a barrel shorter than 14.5 inches (which most of us probably aren’t shooting, as it’s below the legal minimum barrel length for civilian firearms).
Bottom line: Never fire a 5.56 NATO cartridge out of a gun that is marked .223 Rem. — it’s not safe. It is safe to fire a .223 Rem. cartridge out of a gun marked 5.56 NATO, but you might suffer some velocity and accuracy loses. As always, if you have any doubt, just don’t load a firearm with any ammo other than what’s stamped on the gun.