The .223 Remington is a sporting cartridge with the same external dimensions as the 5.56x45mm NATO military cartridge. It is loaded with a .224" diameter, jacketed bullet, with weights ranging from 40 up to 90 grains, though the most common load by far is 55 grains.

The primary differences between .223 Remington and 5.56 x 45 mm (NATO) are that .223 Remington is loaded to lower pressures and velocities compared to 5.56 NATO and the 5.56 NATO chamber has a longer leade. .223 Remington ammunition can be safely fired in a 5.56 NATO chambered gun, but the reverse can be an unsafe combination. The additional pressure created by 5.56 NATO ammo will frequently cause over-pressure problems such as flowing brass, difficult extraction, or popped/punctured primers, but in extreme cases, could damage or destroy the firearm. Chambers cut to .223 Remington specifications have a shorter leade (throat) area as well as slightly shorter headspace dimensions compared to 5.56 NATO "military" chamber specs, which contributes to the pressure issues.

While the 5.56 NATO and .223 Remington cartridges are very similar, they are not identical. Military cases are made with thicker brass in the web area than commercial cases, which reduces the powder capacity (an important consideration for handloaders), and the NATO specification allows a higher chamber pressure. Test barrels made for 5.56 NATO cartridge measure chamber pressure at the case mouth, as opposed to the SAAMI (Sporting Arms and Ammunition Manufacturer’s Institute) location. This difference accounts for upwards of 20,000+ psi difference in pressure measurements. That means that advertised pressure of 58,000 psi for 5.56 NATO, is around 78,000 psi tested in .223 Remington test barrels. SAAMI .223 Rem Proof MAP is 78,500 psi so every 5.56 NATO round fired is basically a proof load, potentially very dangerous. The 5.56 NATO chambers, also known as mil-spec chambers, have a longer leade, which is the distance between the mouth of the cartridge and the point at which the bullet engages the rifling of the barrel. The .223 Remington chambering, known as the "SAAMI chamber", is allowed to have a shorter leade, and is only required to be proof tested to the lower SAAMI chamber pressure. To address these issues, various proprietary chambers exist, such as the Wylde chamber, used by Rock River Arms or the Armalite chamber, which are designed to handle both 5.56 NATO and .223 Remington equally well.

Using commercial .223 Remington cartridges in a 5.56 NATO chambered rifle should work reliably, but generally will not be as accurate as when fired from a .223 Remington chambered firearm due to the excessive leade. Using 5.56 NATO mil-spec cartridges (such as the M855) in a .223 Remington chambered firearm can lead to excessive wear and stress and even be unsafe, and the SAAMI recommends against the practice. Some commercial fireams marked as ".223 Remington" are in fact suited for 5.56 NATO, such as many commercial AR-15 variants and the Ruger Mini-14, but the manufacturer should always be consulted to verify that this is acceptable before attempting it. Signs of excessive pressure (such as flattening or puncturing of the primers) should also be looked for in the initial testing with 5.56 NATO ammunition.