I use it all the time when I am towing except in cities or congestion. I have a 2008 F250 4X4 Diesel and have 135000 + miles. Tow in OD and Tow/Haul mode. No problems yet with tranny, engine, or differential.
Before the 2008 F250 I had a 2001 F250 Diesel and had 150000 miles on it when I sold it and use the cruise all the time when towing. That being said for the pickups, I always paid close attention when I was using the cruise especially in hills with a lot of up and down situations. In the mountains I used it off and on depending.