The moss family Orthotrichaceae is still poorly known in the southern extreme of South America. This is especially true regarding the morphological variability, geographical distribution, and ecological affinities of the species restricted to the Andean-Patagonian area. These deficiencies are addressed for Orthotrichum gigantosporum Lewinsky, one of the least known and most interesting endemics of the area. After examining the rich collections made by our team in southern Chile and Argentina, we have found numerous new localities for the species. Orthotrichum gigantosporum has proven to be a widespread moss in the forests and scrublands of the northern sector of the Andean-Patagonian area. In the light of new morphological data, an updated description of the species is presented and the characteristics that allow its differentiation are discussed and illustrated. The ecological data obtained on the populations also help to characterise the distribution of this moss in relation to various environmental factors. An updated list of the accepted species of Orthotrichaceae present in the Andean-Patagonian area is also provided, facilitating an estimate of endemicity rates within each genus.