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: The purpose of this study was to compare two commercially available specular microscopes (Tomey EM-4000 and Nidek CEM-530) in a real-life clinical setting in terms of intra- and interdevice variability. The study was conducted on all patients seen in a clinical practice specializing in anterior segment pathologies, regardless of the purpose of their visit. : In total, 112 eyes of 56 patients (age 23-85 years old) were included in the study. Each eye was measured three times with each device (for a total of six measurements), and results for central corneal thickness (CCT) and corneal endothelial cell density (ECD) were recorded. The results were then evaluated with the D'Agostino-Pearson normality test and compared with a Wilcoxon signed-rank test, -test, ANOVA or Mann-Whitney test for intra- and interdevice variability. : Both specular microscopes produced very reliable reproducible intradevice results: The Tomey EM-4000 measured an ECD of 2390 ± 49.57 cells/mm (mean ± standard error of mean); the range was 799-3010 cells/mm. The determined CCT was 546 ± 5.104 µm (mean ± standard error of mean [SEM]); the range was 425-615 µm. The measurements with the Nidek CEM-530 revealed an ECD of 2417 ± 0.09 cells/mm (mean ± SEM); the range was 505-3461 cells/mm (mean ± SEM). The mean CCT detected was 546.3 ± 4.937 µm (mean ± SEM); the range was 431-621 µm. The interdevice differences were statistically significant for both parameters, ECD ( = 0.0175) and CCT ( = 0.0125) ( < 0.05). : The Nidek CEM-530 and the Tomey EM-4000 both produced reliable and reproducible results in terms of ECD and CCT. The absolute measurements were statistically significantly different for CCT and ECD for both devices; the Nidek produces slightly higher values.