Duke's first full season with the Pirates in 2006 was as the new team ace, anchoring a very young rotation with Ian Snell. Duke had a number of good starts in the first half of the season, but many of them were undone by the Pirates' weak bullpen and lack of run support for Duke. The second half of 2006 was a re-emergence of the Duke who had dazzled Pittsburgh with his stuff from the previous year, and, on a side note, it was the first time the Pirates had compiled a winning record for a half of a season since 1992. Duke recorded 2 complete game efforts, the only 2 that Pittsburgh had all season. His first was a shutout of the Chicago Cubs on May 2, but he only had 2 strikeouts and a walk. His better effort was on August 11 against the St. Louis Cardinals. While he scattered 8 hits, Duke only allowed 1 run (it was earned), recorded no walks and 7 strikeouts. Duke also threw 11 fewer pitches than his previous complete game effort, and recorded 14 ground-ball outs. Duke's final line for the 2006 season was 10–15 with a 4.47 ERA and 117 strikeouts against 68 walks. During the 2006 season he led the National League in hits allowed, with 255, and his 15 losses were third-most in the league. Duke also became the first Pirates starter since Kris Benson in 2000 to throw more than 200 innings, with 215 and 1/3 innings pitched.