After the 2009 season, the Cardinals added Ottavino to their 40-man roster.[9] He began the 2010 season with Memphis.[11] On May 29, 2010, Ottavino made his major league debut for the Cardinals as a starter. He appeared in five games for the Cardinals in 2010, three of them starts.[12] After the 2010 season, the Cardinals outrighted Ottavino off of their 40-man roster.[13] He pitched for Memphis in 2011, and the Cardinals re-added him to their 40-man roster after the season.[14]
In 2013, Ottavino switched his uniform number to 0.[16] Despite posting a 5–1 win–loss record, his earned run average (ERA) was close to 5.00 in 79 innings. In 2013, Ottavino appeared in 51 games, pitching in 78.1 innings and lowering his ERA from the previous season by two runs, registering an ERA of 2.64 for the Rockies. In 2014, Ottavino went 1–4 with a 3.60 ERA in a career high 75 games.
After closer LaTroy Hawkins struggled to open the 2015 season, Ottavino was named the new closer.[17] On May 4, 2015, it was revealed that Ottavino had a partially torn ulnar collateral ligament in his right elbow,[18] which required Tommy John surgery, ending his 2015 season.[19]
After the 2015 season, the Rockies and Ottavino agreed on a three-year contract worth $10.4 million.[20] Ottavino began the 2016 season on the disabled list.[21] After returning, he completed 37 scoreless appearances, in 31 innings pitched, which set a Rockies' franchise record.[22] In 2018, he was 6–4 with a 2.34 ERA, and shared the major league lead in holds, with 34.[23]
Following the 2017 season, Ottavino rented a vacant storefront on St. Nicholas AvenueinHarlem from his father-in-law which he converted into a pitching lab. In the lab, he and other local players at lower levels of the sport used technology and data to develop pitches and hone their craft.[24]
On January 24, 2019, the New York Yankees signed Ottavino to a three-year contract worth $27 million.[25] Ottavino became the first Yankee in team history to wear uniform number 0, the last single-digit number not retired by the Yankees.[26] During the 2019 season, Ottavino appeared in 73 games for the Yankees, all in relief, pitching to a 6–5 record with 1.90 ERA and 88 strikeouts in 66+1⁄3 innings pitched.[27] During the shortened 2020 season, he made 24 appearances, all in relief, with a 5.89 ERA and 2–3 record with 25 strikeouts in 18+1⁄3 innings pitched.[27]
On January 25, 2021, the Yankees traded Ottavino and minor league pitcher Frank German to the Boston Red Sox for cash considerations or a player to be named later; it was only the second trade between the rivals since 1987.[28] During the regular season, Ottavino made 69 appearances for Boston, all in relief, compiling a 7–3 record with 11 saves and 4.21 ERA. He struck out 71 batters in 62 innings.[27] In the postseason, he made five relief appearances, allowing one run in four innings, as the Red Sox advanced to the American League Championship Series.[27] On November 3, Ottavino elected to become a free agent.[29]
On March 14, 2022, Ottavino signed a one-year contract with the New York Mets.[30] During the regular season, Ottavino made 66 appearances for the Mets, all in relief, compiling a 6–3 record with three saves and a 2.06 ERA; he struck out 79 batters in 65+2⁄3 innings.[27] In his lone postseason appearance, he allowed one run in one inning pitched during Game 2 of the National League Wild Card Series against the San Diego Padres.[27] The Mets lost the series the next night.
On December 20, 2022, Ottavino re-signed a two-year contract with the Mets worth $14.5 million.[31] He became a free agent following the 2023 season and re-signed with the Mets on a one-year, $4.5 million contract on January 30, 2024.[32]
During his first season with the Yankees, Ottavino resided in his childhood neighborhood of Park SlopeinBrooklyn, New York City, with his wife, Brette, and their two daughters.[1] They currently live in Dyker Heights, Brooklyn.