AIM: To investigate the short and long term corneal biomechanical changes after overnight orthokeratology (OK) and compare them with those occurring in subjects not wearing contact lenses. METHODS: Retrospective case control study enrolling 54 subjects that were divided into three groups 18 subjects each: control group (CG), short term (15 nights) OK (STOK) group, and long term (more than 1y of OK wear) OK (LTOK) group. Corneal biomechanics were characterized using the CorVis® ST system (Oculus), recording parameters such as time [first/second applanation time (AT1, AT2)], speed [velocity of corneal apex at the first/second applanation time (AV1, AV2)], and amplitude of deformation (AD1, AD2) in the first and second corneal flattening, corneal stiffness (SPA1), biomechanically corrected intraocular pressure (bIOP) and corneal (CBI) and tomographic biomechanical indices (TBI). RESULTS: Significantly lower AD1 and standard deviate on of Ambrosio’s relational average thickness related to the horizontal profile (ARTh) values were found in the OK groups compared to CG (P<0.05). Likewise, significantly higher values of CBI were found in STOK and LTOK groups compared to CG (P<0.01). No significant differences between groups were found in integrated radius index (P=0.24), strain stress index (P=0.22), tomographic biomechanical index (P=0.91) and corneal stiffness parameter (SPA1, P=0.97). Significant inverse correlations were found between corneal thickness and CBI in STOK (r= -0.90, P<0.01) and LTOK groups (r=-0.71, P<0.01). CONCLUSION: OK does not seem to alter significantly the corneal biomechanical properties, but special care should be taken when analyzing biomechanical parameters influenced by corneal thickness such as amplitude of deformation, ARTh or CBI, because they change significantly after treatment but mainly due to the reduction and pachymetric progression induced by the corneal molding secondary to OK treatment.