PURPOSE To investigate the feasibility of correcting ocular higher order aberrations (HOAs) in keratoconus (KC) using wavefront-guided optics in a scleral lens prosthetic device (SLPD). METHODS Six advanced KC patients (11 eyes) were fitted with an SLPD with conventional spherical optics. A custom-made Shack-Hartmann wavefront sensor was used to measure aberrations through a dilated pupil wearing the SLPD. The position of SLPD, that is, horizontal and vertical decentration relative to the pupil and rotation were measured and incorporated into the design of the wavefront-guided optics for the customized SLPD. A submicron-precision lathe created the designed irregular profile on the front surface of the device. The residual aberrations of the same eyes wearing the SLPD with wavefront-guided optics were subsequently measured. Visual performance with natural mesopic pupil was compared between SLPDs having conventional spherical and wavefront-guided optics by measuring best-corrected high-contrast visual acuity and contrast sensitivity. RESULTS Root mean square of HOA in the 11 eyes wearing conventional SLPD with spherical optics was 1.17 ± 0.57 μm for a 6-mm pupil. Higher order aberrations were effectively corrected by the customized SLPD with wavefront-guided optics, and root mean square was reduced 3.1 times on average to 0.37 ± 0.19 μm for the same pupil. This correction resulted in significant improvement of 1.9 lines in mean visual acuity (p < 0.05). Contrast sensitivity was also significantly improved by factors of 2.4, 1.8, and 1.4 on average for 4, 8, and 12 cycles/degree, respectively (p < 0.05 for all frequencies). Although the residual aberration was comparable to that of normal eyes, the average visual acuity in logMAR with the customized SLPD was 0.21, substantially worse than normal acuity. CONCLUSIONS The customized SLPD with wavefront-guided optics corrected the HOA of advanced KC patients to normal levels and improved their vision significantly.