Cook made his debut, against the Chicago Cubs, pitching two innings and allowing a home run.

He would make his first start, against the San Francisco Giants, pitching six innings while allowing four walks in a no decision.

[3] After posting an ERA of over 5.00 through 14 starts, Cook was demoted to Triple A in exchange for Denny Neagle, who had come out of his rehab assignment.

Cook saw his 2004 season come to an abrupt end when it was discovered that he suffers from pulmonary embolism, or blood clots.

[5] On September 10, Cook underwent extensive surgery at a St. Louis hospital, during which the first rib on his right side was removed to relieve compression on a major blood vein.

Cook stayed on the disabled list until July 30, when he gave up seven runs and eleven hits in 41⁄3 innings of a 9–2 loss to the Philadelphia Phillies at Coors Field.

[7] His first 2005 victory came in an 11-2 decision over the Milwaukee Brewers on August 15, when he pitched six innings and gave up two runs and nine hits.

[6] After battling numerous injuries and inconsistency during his first three years, Cook stayed in the rotation throughout the season, posting an ERA of 4.23 in 32 starts for the Rockies, finishing 9–15.

Despite pitching half his games in Coors Field, Cook's ERA was a run higher on the road (4.62) than at home (3.96).

In a 2008 game against the San Diego Padres, Cook threw a complete-game shutout while hurling just 79 pitches.

On May 1, the day he chose to exercise his opt-out clause, it was announced he would be promoted to Boston to start in place of the injured Josh Beckett.

On June 29, 2012, against the Seattle Mariners, Cook threw a complete-game shutout, allowing just two hits and walking none over 81 pitches, notching the 74th victory of his career.

[22] On January 16, 2013, Cook signed a minor league deal with an invitation to spring training with the Philadelphia Phillies.

He signed to play with Colorado Springs Sky Sox, the Rockies Triple A Baseball team.