They found 173 reports of accidents and injuries in people taking Chantix. They also found 397 cases of psychotic behavior and another 227 involving suicidal behavior.
Hundreds of cases of severe skin swelling, heart problems and diabetes were also reported.
The Federal Aviation Administration said 150 pilots and 30 air traffic controllers used Chantix, but it was unclear how many of the pilots worked for airlines.
While the FAA was not aware if any accidents linked to use of the drug, "it's prudent to deem the drug no longer acceptable for use," agency spokesman Les Dorr said.
The new study prompted the Health Research Group of consumer advocacy group Public Citizen to call for stronger "black box" warnings on the drug's packaging.
(Additional reporting by Ransdell Pierson in New York and John Crawley in Washington; Editing by Tim Dobbyn)