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On a 14 you need brackets to raise the fender. On earlier bikes up to 13 just elongate the rear mounting holes in the fender. I run a 21" on my glide and love the ride. It seems to fall into the corners easier. The Michelin Commander II tire I am running makes a big difference in handling as well.
The 21 front wheel sits the front of the bike a little bit higher than stock, about 1". Some people say the steering feels a little slower but on a bike with a high center of gravity such as a bagger I feel no difference.
For clarification purposes, the wheel fits without enlarging the holes but this is done as a precautionary measure to allow for growth in the height of the tire while riding at speed.
If it is a CVO Road Glide no it won't fit without lift brackets. Other CVO models and non CVO models will fit without brackets. I always go up two drill bit sizes larger to allow the fender to be "rocked" for clearance.
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