Which ISS expedition first operated with a six-person crew?

Expedition 20 was the first ISS expedition to operate with a six-person crew. The milestone began in May 2009, when three new crew members arrived aboard Soyuz TMA-15 and joined the three astronauts already living aboard the station. Increasing the permanent crew from three to six greatly expanded the time available for science and station maintenance.

The six-person crew represented all five major ISS partner agencies: NASA, Roscosmos, the European Space Agency, the Japan Aerospace Exploration Agency, and the Canadian Space Agency. Its members were Gennady Padalka, Michael Barratt, Timothy Kopra, Koichi Wakata, Roman Romanenko, and Frank De Winne. Padalka commanded the expedition, becoming the first commander of two consecutive ISS expeditions.

Expedition 19 preceded the full six-person arrangement, although some of its members remained aboard when Expedition 20 began. Expedition 21 followed Expedition 20, so the numbering can cause confusion. The key distinction is that Expedition 20 marked the start of routine six-person ISS operations, a configuration that became standard for many later expeditions.