Visual rehabilitation following penetrating keratoplasty is the primary indication for approximately 15% of all scleral lens fittings. Since corneal biomechanics are altered following penetrating keratoplasty, the aim of this study was to quantify changes in anterior corneal optics following short-term scleral lens wear in eyes with corneal grafts. Scheimpflug images were obtained before and after a period of scleral lens wear (mean 6.3 ± 1.4 h), from eyes that had previously undergone penetrating keratoplasty (10 eyes of nine participants, mean age 31 ± 9 years). Corneal power and thickness data were examined over the central 6 mm, including regional analyses of the central (0-3 mm) and the mid-peripheral cornea (3-6 mm annulus) using customised software to deterime corneal power vectors M (best fit sphere), J0 (90/180 astigmatism) and J45 (45/135 astigmatism). Anterior corneal aberrations were extracted using corneal elevation data. Corneal power vector J45 increased following lens wear (by 0.22 ± 0.05 D, p = 0.003) across the central 6 mm, while M displayed regional variations following lens wear indicating larger changes further from the corneal centre (p = 0.004). The change in corneal power vector M was also correlated with the magnitude of central corneal swelling (r = 0.65, p = 0.04). The anterior corneal aberration terms of oblique astigmatism, hoirzontal coma, and spherical aberration also varied following lens wear (all p ≤ 0.01). The mean change in the corneal spherocylinder derived from the elevation data following lens wear was +0.14/-0.54 × 44 for a 6 mm corneal diameter. Clinically significant alterations in anterior corneal topography and higher order aberrations were observed following short-term scleral lens wear in eyes that had undergone penetrating keratoplasty. Spherocylindrical changes were approximately double the magnitude and more oblique in orientation compared to previous reports of healthy eyes. Changes in corneal power vector M may be related to epithelial corneal oedema.