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Not longer after polls closed in Mississippi on Tuesday evening, multiple news networks projected that the real-estate developer would win the state.
Trump likely earned the majority of the state's 40 GOP delegates.
Shortly after Fox News called Mississippi for Trump, he thanked his supporters in a tweet.
His win came as his Republican rivals have angled to keep Trump from winning the 1,237 delegates he needs to lock up the nomination and avoid a fight at the convention.
Three other states are hosting GOP primary contests on Tuesday: Michigan, Idaho, and Hawaii.