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DeFalco made his first appearance in the mission "Fallen Angel", JSOC observing recorded footage showing details of his exploits in Pakistan; including executing targets for Menendez, or meeting with Pakistani officials. He is later seen in person midway through the mission while David Mason and Mike Harper are observing Menendez's meeting with ISI officers in Lahore. DeFalco and Menendez have a brief exchange of dialogue where the latter instructs DeFalco to see to the capture of Chloe Lynch, which he states he will see to personally before departing from Pakistan.
DeFalco next appears in the mission "Karma", where he and his mercenaries storm into Cayman Trench looking for Chloe. When David and Harper arrive to the club in an effort to escort Chloe out, DeFalco unexpectedly arrives and begins taking hostages from the crowd, demanding Chloe give herself up in exchange for their lives. After executing a hostage and preparing to kill a second, Chloe hands herself to him. DeFalco secures Chloe and orders his men to open fire on the JSOC operatives. Mason and Harper then pursue him through the city, fighting their way through his men to try and prevent him from escaping with Chloe. His fate beyond this point depends on the actions of the player.
If DeFalco is not killed in "Karma", he appears alongside Menendez during the campaign mission "Odysseus", where he and Menendez succeed in taking over the U.S.S. Barack Obama. He will eventually be killed by Farid, who is in turn killed by the traitor, Javier Salazar.