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Building on the same format used in previous NFL Blitz games, Midway released NFL Blitz 2001 on September 12, 2000. The game was released on a handful of platforms, notably the first and only NFL Blitz release for the Sega Dreamcast. The game was also the first of the series to not be released in arcade-cabinet format, wherein the game has not been released since. Blitz 2001 was the last Blitz release for the original Playstation. A slightly modified version of NFL Blitz 2001 was re-released on the Nintendo 64 as "NFL Blitz: Special Edition".
Gameplay stayed essentially the same to previous Blitz releases. The same animations, mechanics, and A.I. tendencies were carried over from Blitz 2000. There were slight improvements to the physics engine in the Dreamcast release which are noticeable during gameplay.
The Dreamcast release of the game saw notable improvements in almost all aspects of the game including graphic quality, sound, and visual presentation. Player photos and statistics were added to relevant plays in-game, as were higher-resolution player models. Weather effects were added to the game, a feature not seen before. The Dreamcast version also featured a wider-angle camera during gameplay, allowing the player to see more of the field for more effective offense and defense.