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Purpose To compare the corneal endothelial cell density (ECD) before and after cataract surgery in patients with and without pseudoexfoliation syndrome (PEX). Methods In this prospective study, we compared the ECD in 62 PEX patients with 62 patients without PEX (controls). The mean age was 78.3 ± 6.2 years and 77.2 ± 5.9 years, respectively. Patients were examined before and at 6 months, 1 year and 2 years after cataract surgery. The corneal endothelium was examined with confocal microscopy, and the ECD was counted both automatically and semi-manually. Nine patients in the PEX group (15%) and 11 patients in the control group (18%) were lost to follow-up in the 2-year period. Within the PEX and the control groups, we also compared the ECD between patients with and without glaucoma. Results Before surgery, the ECD (semi-manual counting) was 2258 ± 342 cells/mm2 in the PEX group and 2322 ± 321 cells/mm2 in the control group (p = 0.29). There were no significant differences in postoperative ECD between these groups at any visit. After 2 years, the ECD had changed by -679 ± 337 cells/mm2 and -704 ± 484 cells/mm2 , respectively (p = 0.78). The preoperative ECD was lower in eyes with glaucoma compared to eyes without glaucoma, both within the PEX group (p = 0.05) and the control group (p = 0.03). After surgery, there were no differences between eyes with or without glaucoma. Conclusion The ECD was not significantly different in PEX eyes compared with control eyes, neither before nor after cataract surgery. However, there seemed to be a lower ECD in eyes with glaucoma before surgery.