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After missing almost 2 years because of multiple injuries, DeSclafani was activated to start on June 5, 2018 against the Colorado Rockies. In a June 23 game against the Chicago Cubs, DeSclafani hit a grand slam off of Brian Duensing. The last Reds pitcher to hit a grand slam was Bob Purkey, also against the Cubs, in 1959. DeSclafani was the starting pitcher and earned the win as the Reds defeated the Cubs 11–2.

In 2017, DeSclafani experienced pain in his right elbow at the beginning of spring training. He was diagnosed with tendinitis and was immediately shut down. He was later diagnosed with a sprained ulnar collateral ligament of the elbow (UCL), and began the season on the disabled list. The Reds sent him a minor league rehab assignment at the end of July, but a reoccurrence of the tendinitis ended the rehab stint. His UCL had recovered. He went on 60 day disabled list, effectively ending his season without appearing in an MLB game.

DeSclafani began the 2014 season with Jacksonville. The Marlins promoted him to the major leagues to make his debut on May 14 with a win against the Dodgers in Los Angeles. DeSclafani struck out seven and also had two hits in the game. DeSclafani was optioned back to the New Orleans Zephyrs of the Class AAA Pacific Coast League on August 16, 2014, with the return of Henderson Álvarez. During a game against the Milwaukee Brewers on September 11, 2014, DeSclafani was ejected for the first time in his MLB career after intentionally hitting Carlos Gómez with a pitch. The next day, DeSclafani was suspended three games and fined an undisclosed amount by the MLB.

On December 11, 2014, the Marlins traded DeSclafani and Chad Wallach to the Cincinnati Reds in exchange for Mat Latos. DeSclafani earned his first win as a Reds pitcher and, subsequently, the first win for a starting pitcher for the Reds in 2015 with a 3–2 win over the Cubs on April 14, 2015. He pitched in 31 starts for the Reds, finishing with a record of 9–13. The following season, he pitched just in 20 starts after a few stints on the disabled list, he went 9–5.

After the 2012 season, the Blue Jays traded DeSclafani, Adeiny Hechavarria, Henderson Álvarez, Yunel Escobar, Jeff Mathis, Justin Nicolino, and Jake Marisnick to the Miami Marlins, receiving Mark Buehrle, Josh Johnson, José Reyes, John Buck, and Emilio Bonifacio in exchange. DeSclafani pitched for the Jupiter Hammerheads of the Class A-Advanced Florida State League and the Jacksonville Suns of the Class AA Southern League in 2013. He pitched to a 9–6 win–loss record and a 2.65 earned run average across both levels. The Marlins named him their minor league pitcher of the year after the season.

The Toronto Blue Jays selected DeSclafani in the sixth round of the 2011 MLB draft. He received a $250,000 signing bonus. In 2012, he pitched for the Lansing Lugnuts of the Class A Midwest League.

The Boston Red Sox selected DeSclafani in the 22nd round of the 2008 Major League Baseball draft. Rather than accept a signing bonus of about $200,000, he enrolled at the University of Florida, where he played college baseball for the Florida Gators baseball team. In 2010, he played collegiate summer baseball in the Cape Cod Baseball League for the Yarmouth-Dennis Red Sox.

Anthony James DeSclafani (born April 18, 1990) is an American professional baseball pitcher for the Cincinnati Reds of Major League Baseball (MLB). He previously played for the Miami Marlins.