The third seed and 2021 champion looked to be cruising into the last 32 in New York for the seventh year running after moving a break up in the third set against his 69th-ranked opponent.
But O’Connell hit back and then saved two match points in the tie-break as Medvedev grew increasingly rattled, the Russian double-faulting twice to send the contest to a fourth set.
In a sign of Medvedev’s fraying nerves he called the doctor out after the third set, sarcastically replying “Yeah, I lost the set” when asked if he was experiencing any symptoms.
Medvedev regrouped and surged 4-1 ahead, saving three break points in the seventh game as O’Connell received treatment to his knee, before finally sealing victory past 1am local time Friday.
“Tough match. I don’t know why but one moment in the match he decided to play much better. I don’t know why was the reason, but it became much tougher for me,” said Medvedev.
“I had opportunities in the third (set) and I managed to use them in the fourth.
“You kind of don’t know when you get frustrated, you never know you could be. I felt today maybe it helped me a little bit.”
He next plays Argentina’s Sebastian Baez, the world number 32 and winner of 12 matches in a row following his titles at Kitzbuehel and Winston-Salem.
Stay current - Follow FMT on WhatsApp, Google news and Telegram