Background: Radiographs, adjunct to clinical examination are always valuable complementary methods for dental caries detection. Recently, progressing in digital imaging system provides possibility of SOFTWARE designing for automatically dental caries detection.Objectives: The aim of this study was to develop and assess the function of diagnostic COMPUTER SOFTWARE designed for evaluation of approximal caries in posterior teeth. This SOFTWARE should be able to indicate the depth and location of caries on digital radiographic images.Materials and Methods: Digital radiographs were obtained of 93 teeth including 183 proximal surfaces. These images were used as a database for designing the SOFTWARE and training the SOFTWARE designer. In the design phase, considering the summed density of pixels in rows and columns of the images, the teeth were separated from each other and the unnecessary regions; for example, the root area in the alveolar bone was eliminated. Therefore, based on summed intensities, each image was segmented such that each segment contained only one tooth. Subsequently, based on the fuzzy logic, a well-known data-clustering algorithm named fuzzy c-means (FCM) was applied to the images to cluster or segment each tooth. This algorithm is referred to as a soft clustering method, which assigns data elements to one or more clusters with a specific membership function. Using the extracted clusters, the tooth border was determined and assessed for cavity. The results of histological analysis were used as the gold standard for comparison with the results obtained from the SOFTWARE. Depth of caries was measured, and finally Intraclass Correlation Coefficient (ICC) and Bland-Altman plot were used to show the agreement between the methods.Results: The SOFTWARE diagnosed 60% of enamel caries. The ICC (for detection of enamel caries) between the COMPUTER SOFTWARE and histological analysis results was determined as 0.609 (95% confidence interval [CI] =0.159-0.849) (P=0.006). Also, the COMPUTER program diagnosed 97% of dentin caries and the ICC between the SOFTWARE and histological analysis results for dentin caries was determined as 0.937 (95% CI=0.906-0.958) (P<0.001). Bland-Altman plot showed an acceptable agreement for measuring the depth of caries in enamel and dentin.Conclusions: The designed SOFTWARE was able to detect a significant number of dentin caries and acceptable measuring of the depth of carious lesions in enamel and dentin. However, the SOFTWARE had limited ability in detecting enamel lesions.