In a flashback during Unforgiven to his time hunting an Arachne with Samuel Campbell, Sam uses this gun in an attempt to kill the Arachne's victims, including Roy Dobbs. However, the victims survive due to being turned into Arachne's themselves.
In All Dogs Go To Heaven, Sam uses this weapon loaded with silver bullets while hunting a skinwalker pack. With the gun, Sam kills the Skinwalker Pack Leader and one of the Pack Enforcers. Though Sam tries to kill Lucky as well, Lucky escapes before Sam can shoot him.
In The Man Who Knew Too Much, after Castiel broke the Wall, Soulless Sam wielded this gun in his efforts to kill the amnesiac Sam with a soul and regain control of Sam's body. The Sam with a soul was able to arm himself with his Taurus from the Impala's trunk and evaded his soulless self's attempt to kill him through a trick, ultimately killing Soulless Sam.
In Who We Are, after his Taurus was stolen by Arthur Ketch, Sam used this gun during the Assault on the British Men of Letters compound, killing several British Men of Letters operatives and confronting Doctor Hess. To make a point when he refused to work with the British operation anymore, Sam shot the computer Doctor Hess was using to talk with the rest of the organization before Doctor Hess was killed by Jody Mills.
Sam apparently recovers his and Dean's guns from the British Men of Letters compound before it is destroyed as Sam is once more using his Taurus in All Along the Watchtower and Dean has his gun back as well.