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He has also appeared in the second season finale of the television series Scrubs.
In 2007, Reynolds guest-starred as Brendan's friend Hams in the episode "Douchebag in the City" of the TBS sitcom My Boys.
Deadpool featured a reboot of the character, ignoring the events of X-Men Origins: Wolverine, and establishing a new backstory for the character that was closer to the Marvel Comics source material.
The film takes place within the larger X-Men film universe, being made possible by the reset timeline in X-Men: Days of Future Past.
He portrayed Billy Simpson in the YTV Canadian teen soap opera Hillside (1991), Michael Bergen on the ABC sitcom Two Guys and a Girl (1998–2001), Marvel Comics characters Hannibal King in Blade: Trinity (2004), and Wade Wilson / Deadpool in X-Men Origins: Wolverine (2009) and Deadpool (2016), the latter earning him a Golden Globe Award nomination.He then had starring roles in two Dreamworks Animation feature films; The Croods and Turbo, both released in 2013. Reynolds went on to star in low-budget films, The Voices (2014), The Captive (2014), and Mississippi Grind (2015); before having a supporting role in the financially successful biographical film, Woman in Gold (2015).His next role was in portraying Nick Walker in the Universal Pictures film adaptation of Dark Horse Comics' R. Reynolds returned to the thriller genre with Self/Less (2015) where he played a dual role (something he had done before in his career).In 2016, Reynolds found critical and commercial success with Deadpool, a movie that had been in development as early as 2000.After portraying Wade Wilson / Weapon XI, without the name Deadpool, in X-Men Origins: Wolverine, he became heavily involved in the development of a Deadpool film.