It depends on how long you plan to cook them. I prefer to set mine on low and cook them for eight hours. The lower and slower, the better. The slower you cook them, the better the collagen breaks down, which makes the meat tender, juicy, and extra flavorful. As mentioned above, it is possible to cook them too long so keeping them on low just in case the time gets away from you is a good idea. The only reason I would cook them on high is if I was in a hurry. And that would be silly since I am using the slow cooker.