The difference is the amount of powder behind the bullet. The 22-250 is one of the best balanced and most flexible of the high powered 22 centerfires. It is also the most popular of the long range 22 varmint cartridges, effective to ranges of 400 yards or more. The 22-250 also has a reputation for outstanding accuracy and has been used with some success for benchrest shooting. Many individuals that have had experience with both the 22-250 and the 220 Swift report that the former gives significantly longer case life with full loads than the latter. The 22-250's, as with most of the other high powered 22's, is not recommended for use on deer or other medium sized game. The reason, of course, is the light varmint bullets are made to expand quickly and will not offer sufficient penetration on a large animal.