Nicholas D. Wolfwood is a young Christian priest who runs an orphanage some 100 iles south of December City in the anime Trigun (and the manga Trigun Maximum). There isn't much money, so he wanders the deserts and cities trying to raise funds to help the kids, with limited success. He dresses in a quite fashionable suit, and aside from his cross cufflinks one would never think him a priest. He only piece of luggage is an enormous cross that he carries with him almost wherever he goes. It is so heavy it takes three men to lift it ("because it's so full of mercy"), yet he carries it like it were nothing. While on one of these trips, he meets Vash the Stampede, and, knowing nothing about each other, they team up to save a girl who would otherwise have been killed by a piece of lost technology. They grow to be friends, and travel together for some time. He will sometimes carry out his mission on the back of his motorcycle, Angelina.

He is friendly and outgoing, but can also be very hard and pragmatic, to the point of alienating others who believe his actions cross the line. He becomes involved with Millie Thompson, one of the two representatives of the Bernadelli Insurance Society sent to keep an eye on Vash; this affair is cut short by his untimely death.

Wolfwood, in fact, has many secrets. First, he is an expert gunman, and his cross is a giant weapon: it contains 6 large pistols, and can be used as a machine gun and a rocket launcher. At times he lets drop statements that show he knows more about Vash's past than he should, but the extent of it is unknown for many months. It turns out that, while he is Vash's friend and comrade, he is also a member of the Gung Ho Guns, a group of killers working for Vash's insane brother, Knives.

Most of the Gung Ho Guns, Wolfwood included, are not members by choice. In Wolfwood's case, he was given a choice: help Knives get Vash, or watch as the children of his orphanage were killed. Interestingly enough, he himself kills Zazie the Beast, Grey the Ninelives, Rai-Dai the Blade, and Leonof the Puppetmaster, all fellow Gung Ho Guns, with apparently little or no repercussions from the other members. The killing of Rai-Dai was particularly chilling, as the samurai had recently ended up the poorer from an encounter with Vash's angel arm, and was in little shape to defend himself. Wolfwood essentially walked up and shot him in the head, without any show of emotion, compassion, or even interest.

In addition to killing, drinking lots of booze, sleeping with (or chasing after) girls, and being bare-chested quite a bit more often than is probably proper for a priest, Wolfwood smokes (heavily), which is interesting as he is the only major character in Trigun who smokes (contrast with Cowboy Bebop).

Wolfwood's parents died when he was very young, and Wolfwood was raised by an abusive "guardian". Around age 12, he killed this man, and was later trained by Chapel the Evergreen, a Gung Ho Gun. This man carries a cross similar to Wolfwood's. Eventually Wolfwood rebels against the control of Knives, and Chapel is sent to kill him. Wolfwood (just barely) defeats Chapel, but lets him live because he had been swayed by Vash's belief that no one has the right to take life. As Wolfwood turns his back on Chapel, Legato uses his powers to take control of Chapel's gun hand, forcing him to shoot his student (and friend?) in the back. Wolfwood exchanges a few word with Vash (without revealing his injury), and then goes to a church were he dies, holding himself up on his cross.

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