Rafael Nadal defeated John Isner 7-6 4-6 6-3 in the Monte Carlo Masters round of 16 on clay. The result followed the form book — Rafael Nadal came in leading the head-to-head 7–1, defending last year's quarter-final. Rafael Nadal extended the head-to-head to 8–1.
| Date | Tournament | Round | Surface | Winner | Score |
|---|---|---|---|---|---|
| 2022-05-09 | Rome Masters | R32 | clay | Rafael Nadal | 6-3 6-1 |
| 2017-10-02 | Beijing | QF | hard | Rafael Nadal | 6-4 7-6(0) |
| 2017-09-22 | Laver Cup | RR | hard | John Isner | 7-5 7-6(1) |
| 2015-05-10 | Rome Masters | R16 | clay | Rafael Nadal | 6-4 6-4 |
| 2013-08-11 | Cincinnati Masters | F | hard | Rafael Nadal | 7-6(8) 7-6(3) |
| 2011-05-22 | Roland Garros | R128 | clay | Rafael Nadal | 6-4 6-7(2) 6-7(2) 6-2 6-4 |
| 2010-05-09 | Madrid Masters | R16 | clay | Rafael Nadal | 7-5 6-4 |
| 2010-03-11 | Indian Wells Masters | R16 | hard | Rafael Nadal | 7-5 3-6 6-3 |
Averages from each player's recent completed matches (20 vs 20). ATP, WTA & Challenger.