BRD Năstase Țiriac Trophy
Pouille defeated 32nd seed Guillermo García-López in the second round and saved one match point in beating 8th seed David Ferrer in the third round to reach the round of 16 of the Miami Open, where he fell to the No. 18 seed Gilles Simon (0–6, 1–6). Pouille was the beneficiary of a singles main draw wildcard at the 2016 Monte Carlo Masters; he defeated Nicolas Mahut in the first round and the No. 9 seed Richard Gasquet before losing to the No. 8 seed Jo-Wilfried Tsonga (4–6, 4–6) in the third round. In April, the unseeded Pouille reached his first ATP World Tour singles final at the BRD Năstase Țiriac Trophy in Bucharest after defeating three seeded players - Ivo Karlović, Paolo Lorenzi and Federico Delbonis in the second round, quarterfinals and semifinals respectively; he lost the final to the unseeded Fernando Verdasco (3–6, 2–6). Pouille won two singles qualifying matches to reach the singles main draw of the Madrid Open; he saved four match points in beating the No. 12 seed David Goffin in the first round of the main draw.