The trail runs roughly south-west to north-east, and Cape Cod's prevailing summer breeze is south-westerly. That has a consequence people work out too late.
Riding from South Yarmouth towards Wellfleet is usually the downwind direction. It feels effortless. Turning round at Wellfleet after twenty-five miles and riding twenty-five back into a fifteen-knot sea breeze at four in the afternoon is not effortless.
If you are doing an out-and-back, start at the Wellfleet end and ride south-west first, so the tired leg is the assisted one. If you are being collected at the far end, or you have arranged a one-way with a rental shop, ride north-east and enjoy it.
Morning is calmer than afternoon almost every day between June and September, because the sea breeze builds through the day. An early start is worth more here than on most trails.
For distance, be realistic. Twenty-five miles each way is a fifty-mile day, which is a genuine ride for most people on a hybrid with a rucksack. Brewster to Wellfleet and back is roughly thirty, Harwich to Brewster and back around fifteen, and the Nickerson loops turn any of them into a longer or shorter day at will.
In October the trail is at its best: cool air, low sun through the pitch pines, and none of the August congestion.