Purpose. To demonstrate a mathematical method for multi-scalar decomposition of discrete corneal topography height data into a space-scale space using wavelet analysis techniques, and to demonstrate the clinical applicability of these computations in the postkeratoplasty cornea. Methods. Fifty patients with either Fuchs' dystrophy (n = 20) or keratoconus (n = 30) were seen preoperatively, at 3 months, at 1 year (before suture removal) and again at 19 ± 3 months (after suture removal) following nonmechanical trephination with an excimer laser for penetrating keratoplasty. Patients were assessed using corneal topography analysis (TMS-1), subjective refraction, and best-corrected visual acuity (VA) at each interval. Two-dimensional biorthogonal wavelets with the order 6.8 at the scales j = 1–4 revealed the following parameters: root-mean square (RMSDEV) and mean absolute (MEANDEV) deviation and maximum absolute height of the peaks or pitches (MAXPEAK) relative to the reference surface specified with the approximation component of scale j = 4. RMSDEV was correlated with the VA at various follow-up intervals. The multiscalar basis components: roughness, waviness and form were separated and recovered from the wavelet soft thresholding techniques. Peaks and pits within the three-dimensional corneal surface topography were detected and localized using the wavelet hard thresholding techniques. Results. In patients with keratoconus, the RMSDEV and the MEANDEV increased from 4.31 ± 1.25 / 5.98 ± 1.88 µm pre-operatively to the 3 months follow-up (4.98 ± 1.41 / 6.92 ± 2.16 µm) and thereafter decreased continuously to the end of the follow-up (1.87 ± 0.63 / 2.63 ± 1.07 µm), whereas in Fuchs' dystrophy the respective values started at a higher preoperative level (6.36 ± 1.24 / 7.20 ± 2.64 µm) and decreased continuously over time (2.73 ± 1.10 / 3.71 ± 1.05 µm after suture removal). In the keratoconus group, the MAXPEAK was increased at the 3 month postoperative exam (8.78 ± 2.29 µm) when compared to the preoperative value (6.55 ± 2.56 µm); however, it decreased again and returned to the preoperative level after one year (6.34 ± 2.12 µm after suture removal). In Fuchs' dystrophy, the MAXPEAK was unchanged preoperatively (8.26 ± 2.83 µm) to the 3 months follow-up, but decreased continuously to the end of the follow-up period (4.57 ± 1.36 µm). The RMSDEV was significantly lower in keratoconus than in Fuchs' dystrophy pre-operatively (P = 0.01) and after suture removal (P = 0.005) and correlated inversely with VA preoperatively (R = -0.53, P = 0.04 / R = -0.69, P = 0.02), at the 1 year exam (R = -0.61, P = 0.02 / R = -0.52, P = 0.05) and after suture removal (R = -0.73, P = 0.01 / R = -0.66, P = 0.025) in keratoconus / Fuchs' dystrophy. Conclusions. The use of wavelet analysis can provide significant clinical information by separating the raw data into the parameters: “roughness”, “waviness”, “form” and various multiscalar peaks and pits. The RMSDEV, a quantitative measure for corneal irregularity, can be used as a new approach for the prediction of potential visual acuity after penetrating keratoplasty. The decomposition of the surface elevation into fundamental components is crucial for a subsequent mathematically based extraction of clinical parameters or for topography-based flying-spot ablation of irregular corneal astigmatism.