Having been successful with the Tucson Toros, the Astros' AAA club in the Pacific Coast League, Kile entered the majors in 1991, going 7–11 in 22 starts.

In his first major league start on April 24, 1991, Kile had a no-hitter going when he was lifted after six innings by manager Art Howe, who wanted to protect the 22-year-old rookie's arm.

Another strong season was 1997, when he went 19–7, compiled a 2.57 ERA, made the All-Star team again, threw a career-high 255+2⁄3 innings, and pitched four shutouts.

Kile made his first postseason appearance in Game 1 of the 1997 National League Division Series against the Atlanta Braves, giving up only two hits but suffering a hard-luck 2–1 loss.

Kile went 16–11 in 2001, and the Cardinals made the playoffs again, losing to the eventual world champion Arizona Diamondbacks in the NLDS.

[4] Kile threw 227+1⁄3 innings and compiled a 3.09 ERA that season, despite having an injured shoulder which required surgery after the Cardinals were eliminated from the playoffs.

[5] On June 18, Kile pitched in an interleague game against the Anaheim Angels, scattering six hits over 7+2⁄3 innings, allowing one run.

Kile and the Cardinals won the game, 7–2, and moved into first place in the NL's Central Division, a spot they held for the rest of the 2002 season.

[8][9] On June 22, 2002, during pregame warmups for what would have been a day game in Chicago against the rival Cubs, team personnel noted Kile's absence.

[8] Cubs catcher Joe Girardi announced at Wrigley Field that the afternoon's game versus the Cardinals had been cancelled, though he did not give a specific reason.

Later that season, when the Cardinals clinched the Central Division championship in a game against the Astros, teammate Albert Pujols carried Kile's number 57 jersey, on a hanger, to the celebration on the field.

The team put chalk and markers in the Busch Stadium concourses so fans could write similar messages on their caps.

In the All-Star Game, Cardinals pitcher Matt Morris wrote DK 57 on his hands and held them up when they announced his name in honor of his fallen teammate and close friend.