Prime Directive may refer to:
- Prime Directive, the guiding principle of Star Trek's Starfleet
- Prime Directive (role-playing game), by the Amarillo Design Bureau
- Prime Directive (album), an album by the Dave Holland Quintet
- Prime Directive (novel), a Star Trek novel by Judith and Garfield Reeves-Stevens
- Prime directive (RoboCop), four rules governing the behavior of RoboCop
- A fake working title of the Transformers (film series)
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