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The anime series adaptation of the Eyeshield 21 manga consists of 145 television episodes was co-produced by TV Tokyo, NAS and Gallop. It first aired on Japan's TV Tokyo network from April 6, 2005 to March 19, 2008, replacing Prince of Tennis.

The anime series was later licensed in North America by Toonami Jetstream as a joint effort with Viz Media, and aired on December 17, 2007 on its site, but before its completion, the streaming service was shut down. The whole series was streamed in English by Crunchyroll, while Sentai Filmworks licensed the series, with distribution from Section23 Films on DVDs.

Both the manga and anime have been featured at various times in the Top Ten lists of their respective media. The anime has been watched by a large number of television viewers in Japan, helping to raise American football's popularity in the country. Publications for manga, anime and others have commented on the Eyeshield 21 manga, which received positive comments for its artwork and characters, and negative responses to its non-football scenes.

The eyecatches are trivia questions known as "American Football Clinic" asked by Mamori before the commercial break and answered by the Devil Bat (who sometimes adds a little information about it). Later on in mid-series, the segments were commented by Japanese-pro football player, Arima Hayato, explaining various techniques pertaining to different aspects of the game.

Episodes

# Episode Title Air Date
1 The Man With the Lightspeed Legs!
Kousoku no ashi wo motsu otoko (光速の脚をもつ男)
April 6, 2005
2 Let's Play Football!
AMEFUTO yarouze! (アメフトやろうぜ!)
April 13, 2005
3 Blaze a Path Down the Field!
FIRUDO wo nejifusero (フィールドをねじふせろ)
April 20, 2005
4 What I Hold In My Hands!
Sono te ni tsukamu mono (その手に掴むもの)
April 27, 2005
5 Half-Second Bodyguards!
0.5 byo no BODII GAADO (0.5秒のボディーガード)
May 4, 2005
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