Purpose. We report the effect of isotretinoin on corneal topography, corneal thickness, and biomechanical parameters in patients with acne vulgaris. Method. Fifty-four eyes of 54 patients who received oral isotretinoin for treatment of acne vulgaris were evaluated. All patients underwent a corneal topographical evaluation with a Scheimpflug camera combined with Placido-disk (Sirius), ultrasonic pachymetry measurements, and corneal biomechanical evaluation with an ocular response analyzer at baseline, in the 1st, 3rd, and 6th months of treatment, and 6 months after isotretinoin discontinuation. Results. The thinnest corneal thickness measured with Sirius differed significantly in the 1st, 3rd, and 6th months compared with the baseline measurement; there was no significant change in ultrasonic central corneal thickness measurements and biomechanical parameters (corneal hysteresis and corneal resistance factor) throughout the study. Average simulated keratometry and surface asymmetry index increased significantly only in the first month of treatment according to the baseline. All changes disappeared 6 months after the end of treatment. Conclusion. Basal tear secretion and corneal morphologic properties were significantly influenced during the systemic isotretinoin treatment and the changes were reversible after discontinuation. No statistical important biomechanical differences were found to be induced by isotretinoin.