Sector 221-G is a region of space in the Beta Quadrant of the Milky Way Galaxy, bordering both the United Federation of Planets and the Romulan Star Empire. The sector lay between Deep Space 5 and the Romulan Neutral Zone, and was relatively close to the Typhon Expanse. Until 2373, the region was dominated by the Thallonian Empire. (Star Trek: New Frontier novel: House of Cards)

When the Empire collapsed in 2373, the entire sector was thrown into chaos as various rival factions struggled for power. The Redeemers were one of the prominent groups who sought to expand their influence in the region, as was the neighboring Danteri Empire. In response to the turmoil, the Federation sent the USS Excalibur, and later her successor and the USS Trident into Sector 221-G to lend humanitarian aid.

In 2377, Si Cwan, one of the two surviving members of the Thallonian royal family, established the New Thallonian Protectorate, a democratic government dedicated to supporting and rebuilding the former client worlds of the Empire. To help support this effort, the Federation constructed a starbase, Bravo Station, near the new Protectorate's border. (NF novel: After the Fall)

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