The purpose of this study was to compare Schick CDR and Trophy RVGui direct digital radiography (DDR) systems for the ability to detect periapical lesions in human cadaver mandibles. Digital radiographs were exposed of teeth with normal periapical areas and of teeth with artificially prepared periapical lesions using both DDR systems. Three examiners independently viewed the images at two different time periods and estimated which bony state was present. The resulting data were subjected to statistical analysis using a two-way ANOVA. Interexaminer variability was statistically analyzed using Spearman's rho. There was no significant difference in the level of accuracy between the two different DDR systems at either observation period. There was a statistically significant high level of agreement between examiners (p < 0.01). In conclusion, there was no significant difference in the accuracy of detecting artificially prepared periapical lesions between Schick CDR and Trophy RVGui DDR systems.