Multiple warplanes destroyed 83 oil tankers Sunday near Albu Kamal, along Syria's border with Iraq, as part of an ongoing mission to wipe out the oil-smuggling infrastructure that helps fund IS.
At the start of the attack, pilots "fired multiple warning shots to encourage truck drivers to leave the area," the US military's anti-IS mission, Operation Inherent Resolve, told AFP.
"Multiple oil tanker trucks departed the area after the warning shots, and we did not pursue them," officials added.
The Obama administration came under criticism from some Republican lawmakers last year after the Pentagon said it had dropped leaflets warning truck drivers of impending strikes.
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The rationale is that IS presses drivers into service and they are not necessarily IS supporters.
Pilots did not drop warning leaflets in Sunday's attack, which was conducted under Operation Tidal Wave II, named after a World War II mission to bomb oil refineries used by the Nazis.
Civilian casualties fuel outrage and are used as a rallying cry by jihadists, and the military will often call off a strike if the risk of civilian deaths is deemed too high.
But critics have accused the Obama administration of making rules of engagement too restrictive and shackling the military.
In just two strikes last year, coalition planes destroyed about 400 tankers that were lined up in the desert waiting to take on illicit oil.
In those cases, pilots dropped leaflets warning drivers.