Piedmont Airlines Flight 22 was a Piedmont Airlines Boeing 727-22 that collided with a twin-engine Cessna 310 on July 19, 1967, over Hendersonville, North Carolina, United States. Both aircraft were destroyed and all passengers and crew were killed, including John T. McNaughton, an advisor to U.S. Secretary of Defense Robert McNamara. The aircraft were both operating under instrument flight rules and were in radio contact with the Asheville control tower, though on different frequencies. The accident investigation was the first of a major scale conducted by the newly created National Transportation Safety Board. A review of the investigation conducted 39 years after the crash upheld the original findings that had placed primary responsibility on the Cessna pilot.

Piedmont Airlines was a local service carrier, a scheduled carrier in the United States that operated from 1948 to 1989, when it merged into USAir. Its headquarters were at One Piedmont Plaza in Winston-Salem, North Carolina, a building that is now part of Wake Forest University.