Previous studies suggest that certain combinations of coma and astigmatism improve optical quality over astigmatism alone. We tested these theoretical predictions on 20 patients. Visual acuity (VA) was measured under best spherical correction for different conditions: low- and higher order aberrations corrected, in the presence of 0.5 D of induced astigmatism, and adding different amounts of coma to 0.5 D of astigmatism. Measurements were performed for different relative angles between coma and astigmatism and for selected conditions, also through-focus. Adding coma (0.23 μm for 6-mm pupil) to astigmatism resulted in a clear increase of VA in 6 subjects, consistently with theoretical optical predictions, while VA decreased when coma was added to astigmatism in 7 subjects. In addition, in the presence of astigmatism only, VA decreased more than 10% with respect to all aberrations corrected in 13 subjects, while VA was practically insensitive to the addition of astigmatism in 4 subjects. The effects were related to the presence of natural astigmatism and whether this was habitually corrected or uncorrected. The fact that the expected performance occurs mainly in eyes with no natural astigmatism suggests relevant neural adaptation effects in eyes normally exposed to astigmatic blur.