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Purpose To compare the prevalence of endothelial rejection episodes and probability of graft survival after initial and repeat penetrating keratoplasty in keratoconic patients with and without atopy. Methods A retrospective review was conducted of all patients receiving penetrating keratoplasty (PK) for keratoconus at the University of Texas Southwestern Medical Center at Dallas from 1988–2009. Inclusion criteria involved those with both an ICD-9 code for keratoconus and a CPT code for penetrating keratoplasty based on a computer data base search. Patients less than 18 years of age were excluded. These records were then reviewed for a history of atopic disorders. The main outcome measures included the prevalence of endothelial rejection episodes and the probability of graft survival. The probability of corneal graft survival in patients with and without a history of atopy was compared using the Kaplan-Meier method. Results There were 168 grafts in 122 patients. There were 66 (39.2%) and 102 (60.8%) grafts with and without a history of atopy, respectively. Bilateral first grafts were required in 32 patients, 14 and 18 with and without a history of atopy, respectively. The atopic and nonatopic groups had no significant differences with respect to: age, preexisting ocular conditions, concomitant surgical procedures, and length of follow up. Males received first grafts significantly more frequently than females in the nonatopic group (p=0.029); however, there was no gender difference in repeat grafts. There were no significant differences in the prevalence of endothelial rejection episodes after the first (p= 0.716), second (p>0.999) and three of more grafts (p>0.999). Graft survival between the atopic and nonatopic groups did not differ significantly in the first (p=0.881), second (p=0.752) or three or more graft groups (p=.157). Among first grafts in the atopic group, no statistically significant difference in survival existed among patients analyzed with different manifestations of atopy (p=0.061). One episode of allograft endothelial rejection created a statistically significant difference in ultimate graft survival probability in both the atopic (p=0.003) and nonatopic (p=0.002) groups. Conclusion Among keratoconus patients receiving penetrating keratoplasty, there is no statistically significant difference in the prevalence of endothelial graft rejection episodes or probability of graft survival between patients with and without a clinical history of atopy.