The low surface roughness of disposable contact lenses made of a new siloxane-hydrogel loaded with hyaluronic acid is reported, as studied by atomic force microscopy (AFM). Before the wear, the surface is characterized by out-of-plane and sharp structures, with maximum height of about 10 nm. After a wear of 8 h, evidence of two typical morphologies is provided and discussed. One morphology (sharp type) has a similar aspect as the unworn lenses with a slight increase in both the height and the number of the sharp peaks. The other morphology (smooth type) is characterized by troughs and bumpy structures. Wettability and clinical performances are also discussed, the latter deduced by the ocular-surface-disease index (OSDI). The main finding arising from this work is the indication of correlation between the change of the OSDI before and after wear and the lens surface characteristics obtained by AFM. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 101B: 1585–1593, 2013.