Several eastbound lanes of I-40 were closed near Lake Wheeler Road just before 5 p.m., and the road fully reopened at 10:45 p.m.
Sky 5 video from the scene showed the crash involved at least three cars and a cement truck.
Authorities said one man was killed in the crash. No other injuries were reported.
Footage from the scene showed traffic was backed up past U.S. Highway 1 in Cary as a result of the crash.
Authorities did not say what caused the crash or release any information about injuries.
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