I just talked to my son's doctor about this last month actually. He's having a little trouble gaining weight lately. She said to take them 15 minutes before eating so that they're already in the beginning part of the intestines when he starts eating. I told her I hadn't known that and had been giving them to him right before eating, she said it's not a big deal but it could make them more effective so to give it a shot. I don't notice any difference. She also said they work for about an hour. Sometimes if we're on the go I give them to him after, or sometimes if I'm not sure how hungry he is I give him 2 then 1 more if he eats a lot (he's supposed to take 3 Creon 10's). But I've never noticed any difference if he takes them 15 min. before, right before, during, or after!