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The USS Defiant (NX-74205) was the second Federation starship to bear the name, and the prototype of the Defiant-class of starships.

The Defiant had been first designed in 2366 as a new ship to fight the threat of the Borg, although it was officially designated as an escort vessel. The ship had been built but the receding Borg threat, numerous flaws, and the fact that it almost tore itself apart during test cruises convinced Starfleet to put the project on hold. Benjamin Sisko became involved in the project when he transferred to the Utopia Planitia Fleet Yards shortly after the destruction of the USS Saratoga at Wolf 359.

The Defiant was assigned to Deep Space 9 in 2371 and was immediately put to the test when it entered the Gamma Quadrant on a mission to open negotiations with the Founders of the Dominion. The starship came under attack by several Jem'Hadar ships and was boarded. Its crew was held and eventually released but its first encounter with the Dominion would not be its last. The Defiant remained at DS9 and saw extensive action during the Federation-Klingon War and the Dominion War.