Everyone is wondering what the tech billionaire will do with the social media company, and he's already flagged trying to expand its freedom of speech ethos.
However, the co-founder of Microsoft has urged Musk to be careful.
Speaking at an event hosted by The Wall Street Journal, Gates said: "He actually could make it worse."
While that's a fairly savage forecast of Musk's abilities, Gates added that the world's richest man has proven to be formidable in his other business ventures.
"That's not his track record," Gates said. "I mean his track record with Tesla and SpaceX is pretty mind blowing at putting together a great team of engineers and taking the people who work in those fields in a less bold way and really showing them up.
"I kind of doubt that will happen this time, but we should have an open mind and never underestimate Elon."
It's unclear how Musk will change the social media service to give users more power around free speech. However, he's committed to making Twitter the 'town square' of public conversations.
“Free speech is the bedrock of a functioning democracy, and Twitter is the digital town square where matters vital to the future of humanity are debated," he said.
But, Gates has warned Musk that letting people say whatever they want can be dangerous.
Gates urged the Tesla boss to really think about his plans to focus on freedom of speech for Twitter.
"How does he feel about something that says vaccines can kill people or that Bill Gates is tracking people?" Gates said. "Is that one of the things he thinks should be spread?"
However, he added: "I have nothing but positive things to say about Elon. If he makes Twitter worse, I will speak out about that."
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