Background/aim: Keratoconus is described as a bilateral, asymmetric, non-inflammatory corneal ectasia. The purpose of the study was to examine the relation between disease asymmetry and severity in the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study cohort. Methods: Analyses included 1037 keratoconus patients from the CLEK Study baseline examination visit, none of whom had undergone corneal surgery in either eye. Disease asymmetry was determined by taking the difference between eyes for continuous variables. For categorical variables, asymmetry was categorised by whether the variable was present in neither, one, or both eyes. Disease severity was defined using the first definite apical clearance lens (FDACL) technique (a rigid contact lens to measure corneal curvature) from the worse (steeper) eye. Statistical analyses included Pearson's correlation coefficients (continuous variables) and analysis of variance (categorical variables). Results: There were generally weak correlations between asymmetry and severity for low contrast habitual visual acuity (r=0.12, p = 0.0003), high contrast habitual visual acuity (r=0.14, p<0.0001), low contrast best corrected visual acuity (r=0.21, p<0.0001), and high contrast best corrected visual acuity (r=0.29, p<0.0001). Asymmetry in refractive error was more moderately correlated with disease severity (r=0.41, p<0.0001), as was asymmetry in the flat (r=0.61, p<0.0001) and steep keratometric readings (r=0.54, p<0.0001). The average FDACL was significantly steeper in patients who had one eye with Vogt's striae, Fleischer's ring, or corneal scarring compared with the average FDACL when neither eye had these findings. Conclusion: Keratoconus patients with more severe disease are also more asymmetric in their disease status.