PURPOSE: To compare central corneal sublayer pachymetry and biomechanical properties after femtosecond lenticule extraction (FLEX) and small-incision lenticule extraction (SMILE). METHODS: A prospective, randomized, single-masked clinical trial of 35 patients treated for moderate to high myopia with FLEX in one eye and SMILE in the other. Anterior segment optical coherence tomography imaging (Heidelberg Spectralis; Heidelberg Engineering GmbH, Heidelberg, Germany) was used to measure central corneal thickness (CCT) and epithelial, flap/cap, and residual stromal bed thickness centrally. The Ocular Response Analyzer (Reichert Ophthalmic Instruments, Buffalo, NY) was used to assess corneal hysteresis (CH) and corneal resistance factor (CRF). Patients were examined before and 6 months after surgery. RESULTS: Mean decrease in CCT was 105 μ m in FLEX-treated eyes and 106 μ m in SMILE-treated eyes ( P = .70), which is equivalent to approximately 14 μ m/diopters corrected. Mean central epithelial thickness increased 7 ± 6 μ m in FLEX-treated eyes and 6 ± 5 μ m in SMILE-treated eyes ( P = .64). Achieved mean flap/cap thickness was 4 ± 6 μ m from the expected thickness in FLEX-treated eyes and 4 ± 9 μ m in SMILE-treated eyes ( P = .37). CH was reduced 2.7 ± 1.3 mm Hg in FLEX-treated eyes and 3.3 ± 1.2 mm Hg in SMILE-treated eyes ( P = .08). CRF was reduced 4.5 ± 1.2 mm Hg in FLEX-treated eyes and 4.6 ± 1.2 mm Hg in SMILE-treated eyes ( P = .71). CH and CRF were highly correlated with CCT, but not patient age. CONCLUSIONS: In this paired-eye study, the flap-based FLEX and cap-based SMILE resulted in almost identical changes in central corneal sublayer pachymetry and biomechanical properties for moderate to high myopia 6 months after treatment. [ J Refract Surg. 2014;30(2):102–108.]