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Ohio River Valley is a huge American Viticultural Area (AVA) in the central-east of the United States. This 15.5 million-acre (6.3 million-hectare) wine zone covers the catchment of the Ohio River on its south-westerly course through West Virginia, Ohio, Indiana and Kentucky. Ohio River Valley held the esteem of being the largest AVA in the country from its establishment in 1983 until 2009, when the much larger Upper Mississippi Valley AVA was created.

An Ohio River Valley wine label

The Ohio River Valley AVA spans 470 miles (750km) or so along the banks of the river – a distance similar to that which separates London from the Rhone Valley, or the Mosel from Tuscany. This has led many to question its validity as a statement of origin: when criticisms are made of the US system of AVAs, the Ohio River Valley and the Upper Mississippi Valley are the first to be highlighted.

The Ohio River marks the boundary between two climatic regions of the eastern United States: the humid subtropics of the southern states and the colder continental climate of the north. As a result, the AVA is home to fauna and flora of both climate types, and this holds true for its grapevines, which are a mixture of warm- and cool-climate varieties. The vineyards here are planted mostly to hybrid grape varieties such as red Marechal Foch and Baco Noir and white Seyval Blanc and Vidal. There are also vinifera vines found in the Ohio River Valley, notably Chardonnay, Cabernet Sauvignon, Cabernet Franc and Riesling.

The Ohio River Valley is one of several regions that claim to be the birthplace of American viticulture. The first wines were produced in the valley in the early 19th Century, particularly from Catawba, which soon became the area's most important grape variety. The American Civil War of the mid-19th Century saw many of these vineyards neglected, and the arrival of Prohibition in the early 20th Century made viticulture effectively redundant. Winemaking in the Ohio River Valley is only now showing signs of recovering its former strength.

In early 2013, the boundaries of the Ohio River Valley AVA were redrawn to exclude the land within the new Indiana Uplands AVA in southern Indiana. As a result, the size of the AVA was reduced by almost a million acres (400,000ha) – an area larger than at least three-quarters of the AVAs in the United States.