Objective To investigate the influence of the topical anesthetic oxybuprocaine on corneal thickness (CT), corneal epithelial thickness (CET), and corneal uniformity among patients scheduled for corneal refractory surgery. Methods In this prospective self-controlled study, a total of 59 eyes of 30 consecutive patients presenting for SMILE in the Refractive Surgery Center during March 2016 were enrolled. The central (2 mm diameter), para-central (2-5 mm diameter), and peripheral (5-6 mm diameter) CT and CET were assessed by anterior segment optical coherence tomography before and after 30 minutes after the instillation of 0.4% oxybuprocaine prior to SMILE. Each area was divided into 8 regions. Values of the superior-inferior, nasal-temporal, range, and the standard deviation of the CET and CT were used to assess the uniformity of the cornea. Keratometry, astigmatism, eccentricity, central pupil thickness, and the thinnest point of the cornea were recorded by Pentacam. Paired t-test and contour analysis were used to detect anesthetic effects. Results While the CET of 3 eyes of 2 patients was significantly increased after oxybuprocaine, there was no significant effect overall on the CET of the entire study group. Central pupil thickness was 535.6±25.1 µm and 537.7±25.1 µm before and after the use of the topical anesthetic (t=-2.74, P＜0.01). There was a significant increase in CT in the infero-temporal area of the para-central region after oxybuprocaine. The distributions of CT and CET did not change significantly. Eccentricity values before and after oxybuprocaine were 0.56±0.10 diopter (D) and 0.57±0.10 D (t=-2.60, P＞0.05), respectively. There was no significant difference in astigmatism or thickness at the thinnest point before and after the use of the topical anesthetic. Conclusion The topical anesthetic oxybuprocaine had little influence on the thickness and shape of the cornea or corneal epithelium. However, some individuals can have a significant increase in CET after anesthetic eye drops are instilled. This requires a close observation by the surgeons.