Isner, top seed in the event, won 6-4, 7-6 (7-2) over Izak Van der Merwe.
Ryan Harrison of the United States also advanced. Harrison was leading Benjamin Becker 6-4, 3-0 when the German withdrew from their match.
Isner and Harrison will clash in the semifinals Saturday.
Australian veteran Lleyton Hewitt and another American, Rajeev Ram, will meet in the other semi.
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