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The Australian secured a second-round meeting with another Argentinean, No.32 seed Federico Delbonis.
Kyrgios, who had not competed since January's Australian Open, was full of his typical flair, highlighted by 27-15 winners and 12-1 aces.
"When I play good, I'm pretty good," Kyrgios said after the match. "I'm just going back to basics."
🗣 @NickKyrgios said he's feeling fresh after making a winning return to the court at the @BNPPARIBASOPEN in Indian Wells. pic.twitter.com/cID4bt1OrZ— beIN SPORTS (@beINSPORTS_AUS) March 11, 2022
Fabio Fognini made history in his 3-6 6-3 6-3 victory over Pablo Andujar, with his 392th career ATP win clocking up the most ever for an Italian, surpassing Adriano Panatta.
Compatriot Lorenzo Musetti also progressed on Friday (AEDT) with a 6-3 7-5 win over American Marcos Giron.
Rising American talent Jenson Brooksby defeated Roberto Carballes Baena 6-1 6-4, while countryman and wild card Jack Sock brushed aside Juan Manuel Cerundolo 6-1 6-1 in little more than an hour.
Pedro Martinez made light work of Joao Sousa 6-4 7-5, while Tomas Machec got past Alexei Popyrin 6-3 7-5.