Purpose <p>To compare the optical zone decentration and visual outcomes between keratorefractive lenticule extraction (KLEx) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK) in patients with asymmetrical high astigmatism.</p> Methods <p>This prospective study included 76 patients (76 eyes) with myopia and asymmetrical astigmatism greater than 2.00 diopters (D): 40 eyes treated with KLEx and 36 eyes treated with FS-LASIK. Decentralization values were assessed using the tangential curvature difference map preoperatively and 6 months postoperatively. Decentration, astigmatic correction, and visual quality were compared between the two groups 6 months postoperatively.</p> Results <p>At 6 months postoperatively, the vertical decentration for KLEx was greater than FS-LASIK (P=0.014), while no significant differences were found in the horizontal and total decentration between the two surgeries (all P&gt;0.05). Moreover, both surgeries achieved favorable astigmatic correction, with a mean correction index of 0.98 and 1.05 for KLEx and FS-LASIK, respectively. Visual and refractive outcomes, induced total higher-order aberrations, and contrast sensitivity were comparable between KLEx and FS-LASIK (all P&gt;0.05). KLEx induced less spherical aberrations but greater vertical coma than FS-LASIK (all P&lt;0.05). The induction of vertical coma was significantly negatively correlated with vertical decentration. At the same time, no significant correlations were found between the total decentration and induced changes in corneal aberrations in both surgeries (all P&gt;0.05).</p> Conclusion <p>Both KLEx and FS-LASIK were safe and effective for the correction of asymmetrical high astigmatism. However, KLEx induced a greater vertical decentration thus larger vertical coma but less spherical aberration than FS-LASIK.</p>