Dominic Thiem suffered defeat in his first ATP Tour match since June, losing at the Serbia Open to John Millman.
Thiem has been out of action since suffering a right wrist injury and the former world number three was able to claim the second set in his comeback match.
But he could not avoid a 6-3 3-6 6-4 defeat in a contest that lasted two hours and 35 minutes.
Speaking afterwards, Millman said: "It is great to be back here. I was looking forward to coming back and [playing]. All credit to Domi.
"I can't claim it was one of my biggest wins because he is just coming back from injury and I know how hard that is, coming back from three surgeries myself.
"I know it has been tough for Domi but the game is better having him back. Especially on this surface. I have got to take this win because when he gets better and fitter, it is going to be tough."
Next up for the Australian is Miomir Kecmanovic.
NextGen star Jiri Lehecka booked a meeting with second seed Andrey Rublev by beating Henri Laaksonen, while Filip Krajinovic overcame David Goffin.
At the Barcelona Open, fourth seed Cameron Norrie had to come back from a set down to see off Egor Gerasimov, though his 12th seeded fellow Briton Dan Evans lost to Lorenzo Musetti.
There were routine wins for second seed Casper Ruud, sixth seed Diego Schwartzman and 11th seed Lorenzo Sonego.