At Wimbledon, there are no fifth-set tiebreaks, a rule with which Isner is extremely familiar, so one of the players was going to have to break the other's serve at least once in order to reach the final.
And he made it clear Grand Slam tournament organisers should consider a rule change - perhaps introducing a tie-break at 6-6 - to make the deciding set of five-set matches less gruelling.
Ultimately, it was Anderson who prevailed, taking the match 7-6, 6-7, 6-7, 6-4, 26-24.
As the fifth set dragged on and on, the American Isner appeared more visibly exhausted and had to survive more scares on his own serve than Anderson.
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However, Isner was then unable to convert a set point of his own in the tiebreak before 32-year-old Anderson wrapped it up thanks to a netted return. Because of the length of the first match, that semifinal will be played with the roof closed.
That inconsistency was eliminated in an absorbing final set before Anderson produced a moment of magic.
Neither Isner nor Anderson had won a Grand Slam title nor, prior to this week, advanced beyond Wimbledon's fourth round despite a decade of trying.
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Isner and Raonic entered Wednesday night's quarter-final as the two leading players for aces in the tournament at 135 and 117 respectively.
"I don´t really know what to say right now, playing like that in those conditions was really tough for the both of us", said eighth seed Anderson.
Isner, 33, a native of Greensboro, N.C., and Anderson, 32, who was reared in Johannesburg, were longtime rivals at the top ranks of college tennis, when Isner played for Georgia and Anderson, for IL.
Anderson was coming off a huge upset win in the quarterfinals over Roger Federer.
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