Not sure about MDF,but I don't see why not. I used it to fix a rotten section of a trim peice header on my garage door. I didn't catch the way the water was trickling down behind it 'til it had rotted through a bit. I fixed the water intrusion which was coming in behind the aluminum flashing,but over the Tyvek wrap. I then bondoed the heck out of the rotted area after getting down to the "good wood" and painted it. It's been nearly a year and it still looks great and is as hard as a rock.
Steve