221 may refer to:
In time: The year: 221 AD 221 BC
In mathematics:
221 (number)
In geography: Roads: U.S. Route 221 in Virginia
In astronomy: 221 Eos, a main-belt asteroid
In transportation: Aircraft: The Boeing 221 mail plane Rail: 221 series, a type of train in Japan
In weapons: Firearms: The .221 Remington Fireball pistol cartridge
In fiction: 221B Baker Street, the address of Sherlock Holmes Experiment 221, the codename for Sparky, a fictional alien character in the Lilo & Stitch franchise
See also Two to One (1978 album), album by Thelma Houston