PURPOSE: To evaluate the association of scleral contact lens (SCL) use on the risk for keratoplasty for people with keratoconus. METHODS: The electronic health records of patients receiving eye care at the University of Michigan Kellogg Eye Center between August 1, 2012, and December 31, 2018, were reviewed. Patients with a diagnostic code of keratoconus or corneal ectasia, no previous history of keratoplasty, and for whom data were available for both eyes were included. Using a multivariable Cox regression model, associations between SCL use and keratoplasty were tested and adjusted for sociodemographic factors, maximum keratometry, and current contact lens (CL) use. RESULTS: Two thousand eight hundred six eyes met the inclusion criteria. CL use in each eye was 36.2% with no CL, 7.2% soft, 33.9% rigid gas permeable (RGP), and 22.7% scleral. A total of 3.2% of eyes underwent keratoplasty. In the adjusted model, SCL or RGP CL use significantly lowered the hazard of undergoing keratoplasty (HR = 0.19, 95% confidence interval [CI] 0.09-0.39, P < 0.0001 and HR = 0.30, 95% CI 0.17-0.52, P < 0.0001, respectively) when compared with no CL use. Factors associated with increased risk of keratoplasty were black race as compared to white (HR = 1.87, 95% CI 1.10-3.16, P = 0.02), younger age (HR = 0.92 per 5-year increment, 95% CI 0.86-0.99, P = 0.032), and lower socioeconomic status (HR = 1.08 per 5-point increase in the Area Deprivation Index, 95% CI 1.03-1.13, P = 0.0008). Keratoplasty was not associated with sex, insurance, or maximum keratometry. CONCLUSIONS: Physicians should maximize the use of scleral or RGP CL because patients who successfully use CL have almost one-fifth the risk of undergoing keratoplasty.