Region of Southern Denmark (Danish: Region Syddanmark) (German: Region Süddänemark) is an administrative region of Denmark established on Monday 1 January 2007 as part of the 2007 Danish Municipal Reform, which replaced the traditional counties ("amter") with five larger regions. At the same time, smaller municipalities were merged into larger units, cutting the number of municipalities from 271 before 1 January 2006 to 98. The reform was implemented in Denmark on 1 January 2007, although the merger of the Funish municipalities of Ærøskøbing and Marstal, being a part of the reform, was given the go-ahead to be implemented on Sunday 1 January 2006, one year before the main reform.

The regional capital is Vejle but Odense is the region's largest city and home to the main campus of the University of Southern Denmark with branch campuses in Esbjerg, Kolding and Sønderborg. The responsibilities of the regional administration include hospitals and regional public transport, which is divided between two operators, Sydtrafik on the mainland and Als, and Fynbus on Funen and adjacent islands.

Region of Southern Denmark is the westernmost of the Danish administrative regions (Region Zealand being the southernmost).

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