Following the 1975 season, he was dealt to the Houston Astros for two players to be named later (on December 12, 1975, the Reds received reliever Luis Sanchez and third baseman and catcher Carlos Alfonso).

Andújar began seeing more work out of the bullpen in 1978 and earned his first career save on August 25 against the Pittsburgh Pirates.

He was named to his second National League All-Star team and pitched two innings while giving up two runs (one earned).

The Astros won a one-game playoff against the Los Angeles Dodgers, which resulted in Andújar making his first postseason appearance.

After starting the 1981 season at 2–3 with a 4.88 ERA, Andújar was acquired by the St. Louis Cardinals from the Astros for Tony Scott on June 6, 1981,[11] just before the players' strike.

MLB.com Cardinals beat writer Jenifer Langosch wrote in 2013 that it was one of the five best in-season trades in franchise history.

The Cardinals swept the Atlanta Braves in the 1982 National League Championship Series, with Andújar starting and winning Game 3.

The Cardinals and New York Mets became embroiled in a heated battle for the NL East crown that came down to the wire.

In the 1985 National League Championship Series, he was ineffective in his Game 2 start against the Los Angeles Dodgers, which put the Cardinals in a two-game hole.

[23] When umpire Don Denkinger called a ball, Andújar emphatically showed his disagreement and had to be restrained by teammates.

Andújar was so furious after being ejected from Game 7 that he demolished a toilet and sink in the visitor's clubhouse bathroom in Royals Stadium with a bat.

[25] As a result of this and his conduct toward Denkinger, Andújar was fined $500—the maximum permissible amount at the time—and was suspended for the first 10 games of the following regular season.

Andújar was traded from the Cardinals to the Oakland Athletics for Mike Heath and Tim Conroy during the Winter Meetings on December 10, 1985.

Herzog denied that the transaction had anything to do with Andújar winning only one game after August 23 or what transpired during the World Series.

Cardinals general manager Dal Maxvill said that the team needed a catcher after releasing Darrell Porter and having only a barely tested Tom Nieto on its depth chart.

[26] Andújar was to begin the 1986 season serving a ten-game suspension (later reduced to five) for the World Series feud with Denkinger.