On April 17, 2015, Vázquez made his major league debut by coming in to pitch the top of the ninth inning in a 7–2 win over the Philadelphia Phillies. He pitched one inning, allowing two hits and one run while striking out two batters. He went on the disabled list due to gastrointestinal bleeding on April 22. On June 1, the Nationals called up Vázquez to the major leagues from Syracuse. At the end of the season, Vázquez was able to reach 100 miles per hour (160 km/h) with his fastball in relief. In 49 games for the Nationals, he pitched in 48 1⁄3 innings, posting a 2–1 record with a 2. 79 ERA. With Jonathan Papelbon suspended and Drew Storen injured, Vázquez converted two save opportunities during the final week of the season. He finished the season with a 2. 79 earned run average.