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Background: To compare the diagnostic accuracy of three different imaging systems: Direct digital radiography system (DDR-CMOS), four types of filtered images, and a priori and a posteriori registration of digital subtraction radiography (DSR) in the diagnosis of proximal defects. Materials and Methods: The teeth were arranged in pairs in 10 blocks of vinyl polysiloxane, and proximal defects were performed with drills of 0.25, 0.5, and 1 mm diameter. Kodak RVG 6100 sensor was used to capture the images. A posteriori DSR registrations were done with Regeemy 0.2.43 and subtraction with Image Tool 3.0. Filtered images were obtained with Kodak Dental Imaging 6.1 software. Images (n = 360) were evaluated by three raters, all experts in dental radiology. Results: Sensitivity and specificity of the area under the receiver operator characteristic (ROC) curve (Az) were higher for DSR images with all three drills (Az = 0.896, 0.979, and 1.000 for drills 0.25, 0.5, and 1 mm, respectively). The highest values were found for 1-mm drills and the lowest for 0.25-mm drills, with negative filter having the lowest values of all (Az = 0.631). Conclusion: The best method of diagnosis was by using a DSR. The negative filter obtained the worst results. Larger drills showed the highest sensitivity and specificity values of the area under the ROC curve.