My mom is quilting something by hand with a thick poly batting - don't know if it is the highest loft, but sure higher than I like to use, and it is harder to get small stitches, but not impossible to quilt. If you're going for more of a "folk art" look you could probably use a larger needle and perle cotton to do the stitching, and it would work. If you have or can get scraps of batting, try it out on a test swatch first to see how you like working with the thickness.