Okajima was traded to the Hokkaido Nippon-Ham Fighters right before the start of the 2006 season for two position players, and was a valuable lefty setup man for the team, pitching in 55 games, with a 2.14 ERA.

During spring training in 2007, Okajima was asked what he felt about being relatively anonymous while his teammate and countryman Daisuke Matsuzaka's every move was scrutinized.

[8] However, Okajima then proceeded to hold opponents scoreless for nearly two months until the Yankees scored a run off of him via a fielder's choice on May 22.

[9] At the start of the 2007 Red Sox season, injuries and poor performances limited the effectiveness of anticipated setup relievers Mike Timlin and Joel Piñeiro.

Okajima stepped into the role of primary setup man for closer Jonathan Papelbon and quickly became one of the most dominant relievers in the major leagues.

[10] Okajima's scoreless streak from April to May 2007 was the longest by a Red Sox left-hander since Bruce Hurst 20 years prior.

On May 17, 2007, Okajima faced the heart of the Detroit Tigers order for the second time in one day to earn his second major league save.

[16] Following the All-Star break, Okajima continued to pitch solid and reliable relief innings occasionally closing games for the Sox as they held their place at the top of the AL East.

Red Sox management decided to shut him down following this outing to allow Okajima to relieve the physical and mental fatigue of the longer American season.

[18] Okajima's performance really returned in Game 2 of the World Series against the Colorado Rockies, in which he pitched 2⅓ perfect innings in relief of Curt Schilling, striking out four at Fenway Park.

[28] Okajima inked a minor league deal with an invitation to spring training pending a physical on February 11, 2013.

After the 2014 season Okajima considered returning to MLB but instead chose to stay in Japan, signing with the Yokohama DeNA BayStars in December 2014.

[36] Initially, numerous coaches in Japan, such as Tsuneo Horiuchi, attempted to change Okajima's pitching form.

[39] After the 2005 season, Okajima was traded to the Hokkaido Nippon Ham Fighters where he changed his pitching form and reestablished good control.

[40] Okajima's pitches were of lower than average velocity, forcing him to develop a more consistent release point to better control them.

His out pitch in Japan was his sharp rainbow curveball in the 70–75 mph range, which left-handed hitters found hard to hit.

[42] During an April 15 rainout in 2007, Red Sox pitching coach John Farrell tweaked Okajima's changeup delivery.

[39] Former major league slugger Gary Sheffield declared Okajima "one of the most impressive lefties I've ever seen" with "stuff I have never seen before from anybody.