On November 19, 2004, Cartoon Network premiered their second original series produced in Flash: Hi Hi Puffy AmiYumi. The series was created by Sam Register, who at the time, was Cartoon Network's vice president until 2006. The show was very successful during the time of its run, receiving very positive reviews from critics and audiences, scoring the highest rating for a Cartoon Network show aimed at kids 6 to 11, and becoming one of Cartoon Network's most popular original shows during the time, alongside Teen Titans, Codename: Kids Next Door, Foster's Home for Imaginary Friends, Ed, Edd n Eddy, and the Grim Adventures of Billy and Mandy.

While it was a ratings success for Cartoon Network, and as an Annie Award nominee, it only ran for 3 seasons and 39 episodes produced, with only the first 34 aired in the United States. However, prior to the show's cancellation, the crew was planning on producing a season 4 for the series that was actually set to premiere in the Spring of 2007. While it was unknown what would've happened in the fourth season, it actually would continue the events after season 3. The series was originally planned to have 6 seasons and 78 full episodes, running from 2004 to 2009, much like Foster's Home for Imaginary Friends, though plans for a TV movie were unknown.

However, while Cartoon Network ordered a fourth season in 2006, and was supposed to premiere in 2007, the show's crew announced on their blog (puffycrew.blogspot.com) that Cartoon Network had cancelled Hi Hi Puffy AmiYumi after three seasons and 39 episodes due to Sam Register leaving the channel. The reason Sam Register left the channel, which also caused Cartoon Orbit to close down in 2006, was not only that the show was overshadowed by Ben 10, but was also due to management shakeup, and Renegade Animation was hired to do the work on Cartoon Network's first television movie Re-Animated, which Register was very mad about, because of the channel's name. Register would later move over to work at Warner Bros. Animation. Afterwards, the network removed all mention of the series from its website. Despite this, there was a petition online for fans that wanted Cartoon Network to bring the show back.

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