A finalist here in 1993 and semifinalist on two other occasions, Ivanisevic fell, 7-6 (7-4), 6-2, to Radek Stepanek. The second-seeded Croatian lost to a 23-year-old playing in only his seventh main draw event.
Stepanek improved his career match record to 4-6 and reached his first ATP quarterfinal.
In the the next round, Stepanek will play eighth seed Felix Mantilla of Spain, who posted a 7-6 (7-0), 6-4 victory over Oleg Ogorodov of Uzbekistan.
Top seed Yevgeny Kafelnikov of Russia will try to advance to the quarterfinals for the second straight year when he faces his 20-year-old compatriot, Nikolay Davydenko.
In addition, fourth seed Jiri Novak of the Czech Republic faces Anthony Dupuis of France, fifth-seeded Bohdan Ulihrach of the Czech Republic meets Jonas Bjorkman of Sweden, No. 6 Younes El Aynaoui of Morocco goes against Argentina's Franco Squillari, and seventh seed Rainer Schuettler of Germany, the 1999 winner, squares off against Albert Montanes of Spain.
Spain's Fernando Vicente takes on Austrian qualifier Julian Knowle in a battle of unseeded players.
Millions of Getty images now available for free via embed tool
Boston schools pull out free condoms over wrapping complaints