Purpose: To assess the diagnosis-based impact of donor parameters and trephination diameter as predictive factors on corneal endothelial cell density with an exponential regression model after nonmechanical penetrating keratoplasty (PK). Methods: Six hundred thirty-one eyes [291 keratocomis (group I, trephination diameter 8.0 mm); 202 Fuchs' dystrophies (group II, trephination diameter 7.5 mm)-84 PK only (IIa) and 118 triple procedures (IIb); and 138 pseudophakic bullous keratopathies (group III, trephination diameter 6.5-8.0 mm)] were included in this retrospective study. The time course of the endothelial cell density (specular microscope EM 1100, Tomey, Erlangen) after PK was assessed. Endothelial cell density was analyzed in a longitudinal manner considering at least three valid postoperative cell counts (follow-up 29 17 months) with an exponential regression model (minimizing the residuum between observed and predicted endothelial cell count). The following potentially predictive parameters were assessed: donor age (DA), post-mortem time (PM), storage time (ST) and trephination diameter (group III). Results: In the exponential regression model endothelial cell count decreased in I/II/III by 3.1 +/- 24.2% / 12.6 +/- 20.2% (IIa: 8.9 +/- 17.3%, Ilb: 14.8 +/- 22.0%) / 18.7 +/- 27.3 % annually. PM (P=0.16 P=0.10 / P=0.25) and DA (P=0.20, P=0.12 / P=0.16) did not correlate with the cell loss, but ST (P=0.04 P=0.04 / P=0.02) showed a mild correlation, especially in short-term-stored corneas. In group III the trephination diameter (P=0.01) correlated inversely with the cell loss. Between short-term-preserved and organ-cultured donor corneas there was no statistically significant difference in the cell loss in any group. Conclusions: The post-mortem time and the donor age is not associated with a chronic endothelial cell loss after keratoplasty, whereas a long storage time may exaggerate the endothelial cell loss. Between short-term-preserved and organ-cultured donor corneas there was no difference in the time gradient. In bullous keratopathy patients a larger trephination size reduces the chronic endothelial cell loss.