© 2016 Taylor & Francis.Abstract: Purpose: The aim of this study was to investigate the sensitivity, specificity, and accuracy of The Cone Location and Magnitude Index (CLMI) in keratoconus diagnosis. Methods: 301 eyes of 159 keratoconus patients and 394 eyes of 265 refractive surgery candidates as a control group were enrolled in this retrospective clinical study. CLMI was compared with keratometric corneal topography parameters, wavefront aberrations, and pachymetry data derived from optical coherence tomography using independent sample t-tests and ROC curves. Logistic regression analysis was applied to determine the most accurate parameter in keratoconus diagnosis. Pearson’s correlation analysis was used to determine the correlation between CLMI and the other measurements. Results: Average axial CLMI (aCLMI) was 8.19 ± 6.15 D in the keratoconus group and 0.83 ± 0.62 D in the control group (p = 0.001). aCLMI had the greatest sensitivity (89%), specificity (94%), and accuracy (92%) for the keratoconus diagnosis at the best cut-off point of 1.82 according to the ROC curve. Logistic regression analysis selected aCLMI as the most accurate measurement among the other parameters (accuracy 92.8%). aCLMI showed strongest correlations with coma-like aberrations (r = 0.881), total high-order aberrations (r = 0.858), and vertical coma (r = −0.814), respectively. Conclusion: CLMI is a robust index for screening keratoconus with high sensitivity, specificity, and accuracy.