The .45 Long Colt (EF Auto Ejecting, Double Action) is Vash and Knives' weapon of choice. The .45 Long Colt cartridge was a low impact cartridge developed at the turn of the 20th century due to its use of black powder. This makes the range and penetration depicted in the anime conflict with real-life performance of the cartridge. On the other hand, modern-day loadings with modern smokeless powders can produce ballistic properties equal or even surpassing that of a 44 magnum. These guns aren't based on normal revolvers, but are most likely a mash-up of various features from real-world revolvers. Such as the break top reloading from a Smith and Wesson Schofield revolver and the bottom of the cylinder firing of a Mateba revolver. The distinct profile and top-placed luger closely resembling the Mateba 2006m, which was introduced in 1990 and also appears in Ghost In The Shell.

The two depicted in the series are unique in design as both were built by Knives to be used in two separate stages. The first, described above in further detail, is a simple .45 colt Break Action Revolver. The second stage for each of these weapons is known as The Angel Arm. Each gun is designed with a miniature Plant contained in a break-away portion of the normally solid portions of each pistol. During his 17 years inside the SEED ship, Knives salvaged the needed parts and plant material to fashion this set. When asked what they were by Vash, Knives replied that they were "our Brothers." After Knives had shown Vash the destructive power of the two guns, Vash shot Knives in the leg and ran away taking both Brothers with him. Knives eventually retrieved his from Vash during the July incident, severing Vash's left arm with a shot through his shoulder in the process. Vash's gun is silver, while Knives' gun is black.