I've never used a 22-250 but I do use a .223 and love it. The ammo is easy to find and very cheap. I'm dead nuts at 200 yds. and took a coyote out at 440 yds. I found the bullet only dropped 2 inches at the most! I have heard a lot of good things about the other also. Both are good for long shots but you might want to consider what else you might want to use it for.? The .223 is pretty limitted on weight selection. I'm using 55 gr (most common) but have found them up to 80 some gr. all of which is pretty light. Althogh, I did take out a deer at 300yds with a soft tip 65 gr a few years ago. Just wanted to see what it would do. She didn't go but 75 yds tops but a larger and heavier tip would have left it where it stood. What ever you do I would suggest a bi-pod and good scope. Good luck!!