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The ISU-122 (acronym of Istrebitelnaja - or Iosif Stalin-based - Samokhodnaya Ustanovka 122) was a Soviet assault gun used during World War II, mostly in the anti-tank role.

The ISU-122 was used as a powerful assault gun, a self-propelled howitzer, and a long-range tank destroyer, the same as with the SU-152 and ISU-152 heavy self-propelled guns in general. However, these vehicles differed in their combat use. The primary application of the ISU-122 was as a tank destroyer, while the SU/ISU-152 tended more towards the assault gun role. With the same hull as the IS-2, the ISU-122 had good armour performance but very good performance with high-explosive rounds. The 122-mm gun had great potential, although the gun's abilities were somewhat reduced by the available projectiles and its lack of accuracy. In 1944, the BR-471 was the sole armour-piercing round available. An improved version, the BR-471B (БР-471Б), was developed in early 1945, but was available in quantity only after World War II ended. In extremis, the ISU-122 engaged enemy heavy armour with OF-471 (ОФ-471) high explosive projectiles. These shells had a mass of 25 kg, a muzzle velocity of 800 m/s, and were equipped with a 3 kg TNT charge. Mechanical shock and explosion was often enough to knock out enemy AFVs without any armour penetration.

For urban combat, ISU-122s were utilized as assault guns, but with a lower efficiency in comparison to the SU/ISU-152. In general, Red Army commanders viewed the ISU-122 as a good assault gun. The OF-471 projectile was powerful enough against unprotected and entrenched infantry, pillboxes, and fortified buildings. In urban combat, the long barrel of the 122 mm cannon sometimes made maneuvering difficult.

Use of the ISU-122 as a self-propelled howitzer was rare, although its maximum range of fire exceeded 14 km. Usually, the ISU-122 delivered indirect fire to the enemy during rapid advances when support from towed artillery was not available.