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The prefecture of Trikala is the second in size and the third most populous of the four prefectures of Thessaly. It is located in the northwestern part of the region and it is the most mountainous prefecture. It is crossed by several rivers, which are tributaries of either Pinios or Acheloos. The economy of Trikala is mainly rural with well-developed animal husbandry and forestry. In recent years, tourism has developed a lot and the main reference point is Meteora, a monument of natural beauty. The city of Kalampaka as well as the villages Elati and Pertouli are also important tourist destinations, particularly during the winter months. The capital of the prefecture is the city of Trikala.

The Municipality of Trikala is the seat of the Regional Unit and has approximately 80.900 inhabitants. It is a city with intense greenery around Litheo River, which is a tributary of Pinios. The banks of the river and the picturesque streets in Varousi and Manavika districts are ideal for walks. The monumental buildings of the city show the long history and how the place has received Byzantine, Ottoman, European influences. The fortress of the city and the clock on the tower are the landmarks of the area. In 2004 the Municipality of Trikala was nominated as the "First Digital City of Greece", and has established high standards in the use of new technologies in public administration and the accessibility of citizens to the Internet, also providing expertise in other municipalities of the country.