PURPOSE: To assess the fellow eye as a predictor for keratoconus progression following bilateral same-day accelerated corneal cross-linking (A-CXL). METHODS: This was a post-hoc analysis of data from a prospective study of bilateral A-CXL for progressive keratoconus between 2013 and 2015. The primary outcome measures were absolute change in maximum keratometry (Kmax) (diopters [D]), relative change in Kmax (%), and A-CXL progression (increase in Kmax 2.00 D). Responses in both eyes were measured by the change in Kmax, with the right eye serving as the "predictor"of progression for the left eye. RESULTS: Three-hundred ninety-two eyes (196 patients) with a mean age of 26.8 ± 7.7 years were included. There was a significant correlation in absolute and relative Kmax change (r = 0.26, P .001 and r = 0.32, P .001, respectively) between right and left eyes. In regression analysis, the only significant predictors of change in Kmax in the left eye were preoperative Kmax of the left eye (P .02) and change in Kmax of the right eye (P.001). Eyes that progressed in the right eye were more likely to progress in the left eye (29.4% versus 4.5%, odds ratio = 8.85, P .001). In multiple regression, right eye progression of greater than 2.00 D was the significant predictor of left eye progression of greater than 2.00 D (odds ratio = 15.15, P .007). CONCLUSIONS: This large-scale study of keratoconus following A-CXL indicates that patients with progression in the right eye were 15.5 times more likely to have progression in the left eye. Patients with progression following A-CXL in one eye should be closely observed due to increased risk of progression in the fellow eye.