The beginning of the end for Aeroperlas came in 2010 when two well-publicized incidents involving ATR 42 aircraft caused Panama's Civil Aeronautic Authority to raise several safety and maintenance issues.

This caused Aeroperlas to suffer serious financial problems and to withdraw all the de Havilland Canada DHC-6 Twin Otters from the fleet, which were sold to other airlines or scrapped.

In February 2012, hundreds of people from the Ngobe-Bugle tribe blocked several points of the Pan-American Highway in Panama for almost a week, protesting against a mining project in Cerro Colorado.

This caused major disruptions in traffic to the extent that the Minister of Tourism at that time, Salomoh Shamah, decided to create a nationwide airlift to move people and tourists who were stranded on the highway, at bus terminals and airports, and critical supplies without any cost.

In 2006, according to official numbers published by the Panamanian Civil Aviation Authority, Aeroperlas suffered just one minor incident - the same safety record as Panama's Copa Airlines achieved in the same period.