Basel - French Open champion Stan Wawrinka suffered his eighth first-round defeat at the Swiss Indoors on Wednesday when he slumped to a 3-6, 7-6 (7/2), 6-4 loss to Ivo Karlovic.
Karlovic, the 36-year-old Croatian, sent down 21 aces to take victory over the Swiss second seed after trailing a set and a break.
"I had a poor first set and was missing a lot with my volleys," said Karlovic.
"But I began improving in the second set and got a bit lucky when I converted my break points (in the sixth game at 3-3). After that, things started going my way."
Karlovic, who had lost five of six previous meetings with Wawrinka, next plays Serbia's Dusan Lajovic.
Wawrinka was disappointed to have let the match slip away.
"It's never easy to lose a match like that, especially since I felt I was playing well and feeling good. I had my chances to take control of the match," said the Swiss.
"After the first set, everything was good, I was playing well. I played really good for two sets, more or less. I had a few mistakes, but it can happen.
"He's playing his best year so far, he's improved his game a lot. He serves amazing and you don't get many chances. Today I got my chances and I didn't take them."
Later Wednesday, Spanish third seed Rafael Nadal was facing Bulgaria's Grigor Dimitrov.
Elsewhere in the opening round, fourth seed Kevin Anderson advanced over Croatian teenager Borna Coric 6-3, 6-2 while seventh seed and last weekend's Moscow champion Marin Cilic beat Basel native Marco Chiudinelli 6-3, 7-6 (7/3).
South Africa's Anderson sent down 29 winners, improving his record in the best season of his career to 45-22.
Jack Sock won an American battle with Denis Kudla 6-4, 6-2 and next faces countryman John Isner, the sixth seed.
Russia's Teimuraz Gabashvili stopped Argentina Leonardo Mayer 7-5, 4-6, 6-4.
In the second round, 2014 finalist David Goffin booked a quarter-final spot with a 6-4, 6-3 win over Adrian Mannarino.
Results from the third day of the ATP Swiss Indoors on Wednesday (x denotes seeding):
David Goffin (BEL x8) bt Adrian Mannarino (FRA) 6-4, 6-3
Rafael Nadal (ESP x3) bt Grigor Dimitrov (BUL) 6-4, 4-6, 6-3
Kevin Anderson (RSA x4) bt Borna Coric (CRO) 6-3, 6-2
Jack Sock (USA) bt Denis Kudla (USA) 6-4, 6-2
Marin Cilic (CRO x7) bt Marco Chiudinelli (SUI) 6-3, 7-6 (7/3)
Teimuraz Gabashvili (RUS) bt Leonardo Mayer (ARG) 7-5, 4-6, 6-4
Ivo Karlovic (CRO) bt Stan Wawrinka (SUI x2) 3-6, 7-6 (7/2), 6-4