The April 21, 2005 Edition of Smackdown is a Professional wrestling television show of the WWE's Smackdown brand, which took take place on April 18, 2005 at the Madison Square Garden in New York City, New York.
- Numbers in parentheses indicate the length of the match.
- (c) refers to the champion(s) heading into the match.
- Booker T vs. The Big Show ended in a no contest in a WWE Heavyweight Title #1 Contendership Tournament First Round Match (5:20)
- Matt Morgan defeated Brett Matthews (1:16)
- Booker T & The Big Show defeated John Bradshaw Layfield & Kurt Angle (13:13)
- MNM (Joey Mercury & Johnny Nitro) (w/ Melina) defeated Eddie Guerrero & Rey Mysterio (c) to win the WWE Tag Team Championship (10:27)
- John Cena defeated Orlando Jordan (w/ Doug Basham) (7:07)