The 2012 Winston-Salem Open was a tennis tournament played on outdoor hard courts.

It was the 44th edition of the Winston-Salem Open, and was part of the ATP World Tour 250 Series of the 2012 ATP World Tour.

It took place at the Wake Forest University in Winston-Salem, North Carolina, United States, from August 19 through August 25, 2012.

John Isner won the singles title.

[2] The following players received wildcards into the singles main draw: The following players received entry from the qualifying draw: The following pair received wildcard into the doubles main draw: The following pair received entry as alternates: John Isner defeated Tomáš Berdych, 3–6, 6–4, 7–6(11–9) Santiago González / Scott Lipsky defeated Pablo Andújar / Leonardo Mayer, 6–3, 4–6, [10–2]