ABSTRACT Purpose To report the successful outcome obtained after fitting a new hybrid contact lens in a cornea with an area of donor-host misalignment and significant levels of irregular astigmatism after penetrating keratoplasty (PKP). Materials and methods A 41-year-old female with bilateral asymmetric keratoconus underwent PKP in her left eye due to the advanced status of the disease. One year after surgery, the patient referred a poor visual acuity and quality in this eye. The fitting of different types of rigid gas permeable contact lenses was performed, but with an unsuccessful outcome due to contact lens stability problems and uncomfortable wear. Scheimpflug imaging evaluation revealed that a donor-host misalignment was present at the nasal area. Contact lens fitting with a reverse geometry hybrid contact lens (Clearkone, SynergEyes Carlsbad) was then fitted. Visual, refractive, and ocular aberrometric outcomes were evaluated during a 1-year period after the fitting. Results Uncorrected distance visual acuity improved from a prefitting value of 20/200 to a best corrected postfitting value of 20/20. Prefitting manifest refraction was +5.00 sphere and .5.50 cylinder at 75°, with a corrected distance visual acuity of 20/30. Higher order root mean square (RMS) for a 5 mm pupil changed from a prefitting value of 6.83 μm to a postfitting value of 1.57 μm (5 mm pupil). The contact lens wearing was referred as comfortable, with no anterior segment alterations. Conclusion The SynergEyes Clearkone contact lens seems to be another potentially useful option for the visual rehabilitation after PKP, especially in cases of donor-host misalignment. How to cite this article Pérez-Cambrodí RJ, Ruiz-Fortes P, Llorens DPP. Reverse Geometry Hybrid Contact Lens Fitting in a Case of Donor-Host Misalignment after Keratoplasty. Int J Kerat Ect Cor Dis 2013;2(2):69-72.