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Ohio River Valley is an American Viticultural Area (AVA) in the eastern portion of the United States, covering 15.5 million acres (6.3 million hectares) along the course of the Ohio River. The boundaries of the AVA start in southern Indiana and encompass parts of both Ohio and Kentucky before finding the zone's eastern limits in West Virginia. Ohio River Valley, established as an AVA in 1983, was the largest in the US until the Upper Mississippi Valley AVA was formalized in 2009.

The Ohio River marks the boundary between two climatic regions: the humid, sub-tropical south-eastern states and the colder continental climate of the north-east. As a result, the AVA is home to fauna and flora of both climate types and this holds true for its grape varieties. The vineyards are planted mostly to hybrids such as red Marechal Foch and Baco Noir and white Seyval Blanc and Vidal. Some Vitis vinifera vines are also found in the Ohio River Valley, notably Chardonnay, Cabernet Sauvignon, Cabernet Franc and Riesling.

For more detailed information about this AVA and its wines, see Ohio River Valley – Ohio.