Used in V.A.T.S., a critical strike results in a brutal uppercut, often sending the enemy (or quite often just the head) into the air.
Of all the Unarmed weapons, Fisto! has the highest base damage, the highest DPS (damage per second), and the highest damage per Action Point value when using V.A.T.S. However, it is little over a third the damage per AP of The Terrible Shotgun, and has a lower MDPS (that factors in critical hits) than the deathclaw gauntlet.
Targets that are below the Lone Wanderer's knees, when the player attacks them with an Unarmed weapon in V.A.T.S., are kicked rather than punched.