Purpose: To evaluate the predictability and accuracy of refractive surgery among adults with myopic anisometropia. Methods: Consecutive cases of myopic eyes that underwent bilateral laser-assisted in situ keratomileusis (LASIK) or bilateral photorefractive keratectomy (PRK) during a 12-year period in a single center were included. Myopic anisometropia was defined as a difference greater than 1.5 D in spherical equivalent between eyes preoperative. Results: A total of 10,046 paired, operated nonamblyopic eyes of 5023 patients were analyzed. Of these, 472 eyes of 236 (4.7%) patients had myopic anisometropia without amblyopia, and 9574 eyes of 4787 patients served as isometropic controls. After refractive surgery, in the anisometropic group the more myopic eye was corrected by +0.47 ± 0.78 (D) more than the contralateral eye (P < 0.0001). Relative to the target refraction, the more myopic eye was overcorrected by 0.21 ± 0.79 D compared with an undercorrection of 0.16 ± 0.60 D in the less myopic contralateral eye (P < 0.0001) and compared with an undercorrection of 0.15 ± 0.62 D in the isometropic controls (P < 0.0001). Additionally, the variability in the correction of the more myopic eyes was significantly higher compared with the less myopic contralateral eyes and isometropic controls (P < 0.0001). These trends were evident both in PRK and LASIK treatments. The effect of anisometropia was found to be independent of the magnitude of preoperative myopia or surgeon identity. Conclusions: The more myopic eye of anisometropes undergoing refractive surgery has lower predictability and accuracy and tends to be overcorrected, whereas the less myopic eye has outcome similar to isometropic controls. These results suggest that refractive surgery nomograms should take into account anisometropia.