Comair Flight 5191, operating a Bombardier CRJ-100, was scheduled for a routine flight from Blue Grass Airport in Lexington, Kentucky, to Atlanta, Georgia. On the morning of August 27, 2006, after pushback from the terminal, the aircraft attempted to take off from the wrong runway, Runway 26, which was not intended for commercial jet departures. This runway was significantly shorter than the standard length needed for the aircraft's takeoff. The flight had wheels up shortly after departure but failed to gain proper altitude due to the insufficient runway length and subsequently crashed into a field just beyond the airport perimeter. Investigators later confirmed that the cockpit crew had misconfigured their navigation settings, contributing to the miscommunication regarding runway usage.

During emergency response efforts, 49 of the 50 passengers and crew members were found deceased at the crash site, with only one survivor, who later provided crucial information for the investigation. The National Transportation Safety Board (NTSB) conducted a thorough investigation into the crash and identified various factors that led to this devastating event. Human factors, including crew error and miscommunication with air traffic control, were highlighted as significant contributing factors to the disaster.

As a result of this incident, significant changes were made within the aviation industry pertaining to runway usage protocols, crew training, and the importance of accurate cockpit navigation systems. The accident raised questions about regional airline safety, crew resource management training, and emergency response preparedness, prompting regulatory bodies to evaluate and enhance safety standards across the industry. Though a moment of tragedy, the lessons learned from Comair Flight 5191's crash have been pivotal in improving aviation safety measures.