Character mistake: In the first scene inside the Prometheus, after she comes out of deep sleep, Vickers asks David for a robe, and asks "how long?" meaning how long have they been asleep. David, a robot, answers "2 years, 4 months, 18 days, 36 hours, 15 minutes." The actual statement from this highly precise robot character would have been "2 years, 4 months, 19 days, 12 hours, 15 minutes."
Character mistake: The ship travels approximately 35 light years, yet Vickers (Charlize Theron) comments they are half a billion miles from Earth. That would barely get them past Jupiter, much less another solar system.
Character mistake: When Millburn introduces himself to Fifield, he has a Southern accent. For the rest of the movie, the accent is gone.
Answer: It's a matter of opinion, but watching the first Alien film gives enough of the necessary back story to understand Prometheus. However, it's possible to watch and understand Prometheus without seeing any of the other four Alien films. I would only recommend watching Alien 1 and 2.
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