This is the single thing that separates a memorable trip round the drive from a disappointing one, and most visitors never hear it.
The impoundments either side of the road are shallow, and the birds that people come to see — spoonbills, ibis, herons, egrets, plovers, willets, whimbrels — feed by probing exposed mud and shallow water. When the tide is low, that mud is a feeding table and the birds gather on it, sometimes in hundreds, within easy range of a pull-out. When the tide is high, the table is submerged, the birds disperse into the mangroves, and you drive four miles past trees.
Aim for the two hours either side of low water. Combine that with the first two hours after opening at 7am, or the last two before closing, and you have the best conditions the refuge offers.
Season is the multiplier. December through March brings the migratory birds down and is when roseate spoonbills and white pelicans are most reliable. A low tide at half past seven on a February morning is as good as this place gets, and it is a completely different experience from the same road at noon in August.