AIM: To evaluate the diagnostic ability of topographic and tomographic indices with Pentacam and Sirius as well as biomechanical parameters with Corvis ST for the detection of clinical and subclinical forms of keratoconus (KCN). METHODS: In this prospective diagnostic test study, 70 patients with clinical KCN, 79 patients with abnormal findings in topography and tomography maps with no evidence on clinical examination (subclinical KCN), and 68 normal control subjects were enrolled. The accuracy of topographic, tomographic, and biomechanical parameters was evaluated using the area under the receiver operating characteristic curve (AUC) and cross-validation analysis. The Delong method was used for comparing AUCs. RESULTS: In distinguishing KCN from normal, all parameters showed statistically significant differences between the two groups (P<0.001). Indices with the perfect diagnostic ability (AUC≥0.999) were Sirius KCN vertex of back (KVb), Pentacam random forest index (PRFI), Pentacam index of height decentration (IHD), and Corvis integrated tomographic/biomechanical index (TBI). In distinguishing subclinical KCN from normal, Sirius symmetry index of back (SIb; AUC=0.908), Pentacam inferior-superior difference (IS) value (AUC=0.862), PRFI (AUC=0.847), and Corvis TBI (AUC=0.820) performed best. There were no significant differences between the highest AUCs within keratoconic groups (DeLong, P>0.05). CONCLUSION: In clinical KCN, all topographic, tomographic, and biomechanical indices have acceptable outcomes in terms of sensitivity and specificity. However, in differentiating subclinical forms of KCN from normal corneas, curvature-based parameters (SIb and IS value) followed by integrated indices (PRFI and TBI) are the most powerful tools for early detection of KCN.