Main article: Bosses
Skeletron Prime is a far more difficult Hardmode version of Skeletron, with the head alone having 28,000 HP (42,000 in Expert Mode). Instead of two hands, it has a vice, laser gun, saw, and cannon. With the head and all limbs combined, Skeletron Prime has 59,000 HP. However, like Skeletron, only the head has to be defeated. Skeletron Prime can be summoned as many times per world as needed, by crafting and using a Mechanical Skull, but it can only be summoned at night. It is more mobile than its predecessor, and it regularly flies offscreen, making targeting more difficult. It is also worth noting that when its head spins, its defense increases, unlike Skeletron, whose defense is dropped to 0 when spinning.
Skeletron Prime will drop Hallowed Bars and Souls of Fright upon being defeated, which are both used to craft many kinds of armor and tools. Like Skeletron, if Prime is not killed before the night ends, it will spin and target the player, generally killing the player in one hit, and it will then despawn afterwards.
In Expert Mode, Skeletron Prime will have 42,000 health for the head, and doubled arm health. Skeletron Prime follows around the same guidelines as Skeletron; it is less resistant to damage after its hands are destroyed, but its skull gains twice the amount of defense compared to normal mode Skeletron Prime when in its spinning attack.