Entering the US Open seeded third, del Potro reached the quarterfinals without dropping a set, defeating Donald Young, Denis Kudla, 31st seed Fernando Verdasco, and 20th seed Borna Ćorić. He then faced 11th seed John Isner, defeating him in four sets to reach his second consecutive US Open semifinal, where he faced top seed and defending champion Rafael Nadal in a rematch of the previous year's semifinal. Nadal retired from the match due to a knee injury after del Potro took the first two sets. With this victory, del Potro advanced to his second Grand Slam final, nine years after his 2009 US Open triumph. He was defeated by two-time champion Novak Djokovic, 6–3, 7–6(7–4) 6–3.