Comair Flight 5191 was a domestic U.S. flight from Lexington, Kentucky, to Atlanta, Georgia, operated on behalf of Delta Connection by Comair. On August 27, 2006, at approximately 6:07 a.m. local time, a Bombardier Canadair Regional Jet flying the route crashed after attempting to take off from the wrong runway at Blue Grass Airport, Lexington. The first officer was the only survivor among the 47 passengers and three crew on board. The flight was scheduled to land at Hartsfield-Jackson Atlanta International Airport at 7:18 a.m. local time.

The flight was sold under the Delta brand, as Delta Flight 5191 (DL5191/DAL5191) and was operated by Comair as Comair Flight 191 (OH191/COM191).

Initial analysis of the flight data recorder and the cockpit voice recorder indicates the aircraft was cleared to take off from Runway 22, a 7,003-foot (2,135 meter) long strip used by most airline traffic at Lexington. Instead, after confirming "Runway 2-2," Captain Jeffrey Clay taxied onto Runway 26, an unlit secondary runway just 3,500 ft (1,067 m) in length and then turned the controls over to co-pilot James Polehinke for takeoff. Based upon a takeoff weight of over 49,000 pounds (22,000 kg), the manufacturer estimated a minimum of 3,539 ft (1079 m) would have been needed for takeoff.

There is no indication either pilot tried to stop the plane, which reached a top speed of 137 knots (158 mph or 254 kph) before rolling off the end of the runway. The aircraft clipped the airport boundary fence, cleared a barbed wire fence, and became airborne after hitting a berm. It then hit a group of trees, separating the fuselage and cockpit from the tail, and came to rest largely intact in an area less than half a mile (0.8 km) from the end of the runway where it burst into flame.

All 47 passengers perished along with two of the three crew members.

The crew consisted of Captain Jeffrey Clay, 35, who was by Comair in November 1999, First Officer James M. Polehinke, 44, who was hired in March 2002, and flight attendant Kelly Heyer, 27, hired in July 2004. Comair president Don Bornhorst stated in a press conference that Clay was very familiar with the aircraft.

First Officer James M. Polehinke was pulled from the wreckage by Lexington-Fayette Police Department Officer Bryan Jared and two airport security workers. As of August 29, 2006, he is in critical condition at the University of Kentucky's Albert B. Chandler Medical Center, where he underwent surgery for his injuries. Officer Jared suffered burns on his arms while pulling him out of the wreckage.

Passengers included Jon Hooker, a former University of Kentucky and Chicago White Sox minor league baseball pitcher, and his wife, Scarlett Parsley; they were married the night before the crash and were on the flight as the first leg of their honeymoon trip to California. Pat Smith, who worked for Lexington's Habitat for Humanity, and was 2004 Humanities National Volunteer of the Year, also perished in the crash.

Canadians Anne Marie Bailey, Lyle Anderson and Christina Anderson were also among the dead, according to Canada's Department of Foreign Affairs. Japan's Foreign Ministry announced that two Japanese, Tetsuya and Nahoko Kono, were killed in the crash.

Only a few friends and family members of the passengers were present at the Atlanta airport at the time of the crash, since most of the victims had planned to connect to other flights en route to their destinations.