 If you liked
Trigun
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 ...then you might like
Yu☆Gi☆Oh! Duel Monsters GX
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Yugioh GX and Trigun starts off with a light hearted and comedic fashion until at some point it gets serious and dreadful which almost makes you want to lose hope. I find Judai and Vash similar where they are very protective but at the same time must face harsh consequences to overcome their obstacles.
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Recommended by SlaughterDagger
They are mainly both similar plot wise : in the start, is the "normal " life. But as the story goes, the past of the main character gets everybody involved, forcing some change in the main character's surrounding and the main character itself.
Small note to make: Yugioh GX focus on the card game. And is rather long compared to Trigun.