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Purpose: To assess the efficacy and safety of corneal wavefront-guided custom laser in situ keratomileusis (LASIK) to correct refractive errors and higher-order aberrations (HOAs) after penetrating keratoplasty (PKP). Setting: Beyoglu Eye Training and Research Hospital, Istanbul, Turkey. Design: Noncomparative case series. Methods: The study comprised consecutive patients who were unable to tolerate spectacles or contact lenses for the correction of anisometropia after PKP and had corneal wavefront-guided custom LASIK. The uncorrected (UDVA) and corrected (CDVA) distance visual acuities, manifest refraction spherical equivalent (MRSE), and corneal HOAs were recorded before and after LASIK. Results: The study evaluated 11 eyes (10 patients). The mean follow-up after LASIK was 24.3 months ± 11.7 (SD) (range 9 to 36 months). The mean MRSE was −2.97 ± 1.66 diopters (D) (range −0.50 to −5.38 D) preoperatively and −0.88 ± 0.96 D (range −2.75 to 0.5 D) postoperatively. The mean total higher-order root mean square (RMS) was 4.65 ± 1.14 μm (range 2.26 to 5.94 μm) preoperatively and 2.71 ± 1.31 μm (range 1.22 to 5.33 μm) postoperatively. Postoperatively, the UDVA improved in 7 eyes and remained unchanged in 4 eyes. The CDVA improved in all eyes postoperatively even cases in which the attempted astigmatic correction was not totally achieved. Conclusions: Corneal wavefront-guided custom LASIK after PKP did not totally correct both refractive errors and HOAs because of the high volume of laser ablation required and inadequate corneal stromal thickness. Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned. [ABSTRACT FROM AUTHOR]