AIM: To compare the wavefront aberrations and corneal surface regularity between dry eye (DE) patients and normal subjects and assess its diagnostic performance for DE measured with OPD Scan-III. METHODS: Fifty right eyes of 50 DE patients and 31 right eyes of normal subjects were included. The examinations for ocular surface including logarithm of the minimum angle of resolution best-corrected distance visual acuity (logMAR BCVA) the ocular surface disease index (OSDI), tear film break-up time (TBUT) and corneal fluorescein staining (CFS). OPD Scan-III was used to measure anterior corneal aberrations including total corneal aberrations, high order aberration (HOA), coma, trefoil, spherical aberration (SA), standard deviation of corneal power (SDP), surface regularity index (SRI) and surface asymmetry index (SAI). Statistical analysis were assessed with nonparametric tests and Spearman's correlations. All parameters were also analyzed for sensitivity, specificity, and receiver operating characteristics (ROC) curves. RESULTS: Wavefront aberrations parameters including total corneal aberrations, HOA, coma, trefoil, and SA in DE group were significantly higher than those in normal group (P<0.001). Corneal surface regularity parameters including SRI and SAI in DE group were significantly higher than both in normal group (P<0.05). All the wavefront aberrations parameters had significant correlations with ocular surface parameters (P<0.05). The logMAR BCVA had positive correlations with SAI and SRI (all P<0.001). CFS scores had positive correlations with SAI and SRI (all P<0.001). All the wavefront aberrations parameters showed good diagnosis sensitivity and specificity, however, the corneal regularity parameters showed only good specificity but poor sensitivity. The cut-off value selected for trefoil in diagnosis DE showed the highest area under the curve (AUC, 0.921) values as compared to the other parameters with sensitivity of 0.955 and specificity of 0.867. CONCLUSION: Wavefront aberrations and corneal surface regularity are increased in DE patients and also correlated with ocular surface parameters. Wavefront aberrations parameters have potential to be indicators to diagnosis and monitor DE.