On 6 June 1985, Douglas C-53D HK-1340 of LACOL Colombia crashed shortly after take-off after the starboard engine failed while the aircraft was on a cargo flight. The aircraft was probably overloaded and it caught fire after crashing into trees. Three of the six people on board were killed.
On 28 May 1993, Douglas C-53D HK-2213 of Transoriente Colombia crashed near Villavicencio after both engines failed shortly after take-off from La Vanguardia Airport on a scheduled passenger flight. Seven of the 29 people on board were killed.
On 30 March 1996, Douglas C-47B HK-2497 of LANC Colombia was damaged beyond repair in a wheels-up landing on approach to La Vanguardia. The aircraft was on a domestic scheduled passenger flight to La Macarena Airport when an engine problem was encountered and the decision was made to return to La Vanguardia.
On 3 November 2010, an explosion took place at the airport warehouse. No casualties were reported. The explosion was caused by a parcel. As a result, several airlines suspended flights from the airport.