Objective—To develop software for automated registration and intensity calibration of serial dental radiographs for the analysis of longitudinal changes in bone density. Methods—Serial dental radiographs were acquired using a positioning device designed to minimize projection divergence. Each radiograph included an image of a standardized aluminium wedge. The radiographs were scanned on a flatbed scanner (AGFA Duo Scan) with a spatial resolution of 300 dpi, and pixel intensity coded in 16-bit grey scale. The intensity was calibrated using serial images of selected areas with defined thickness of the aluminium wedge. A robust B-splines multiresolution registration algorithm was implemented to overcome the acquisition misalignment. Radiographs, taken before and after periodontal therapy, were subtracted to assess bone density evolution. Results—The intensity calibration decreased the maximum intensity variations between serial radiographs from 30±17% to 1±1% (mean±standard deviation), and improved the visual comparison between the radiographs. The registration stage allowed correcting the misalignment of the radiographs on the scanner screen and superimposing the radiography contents. The observed residual motion was about 0.02±0.01 mm. Conclusion—Very user-friendly software was developed. The manipulator needs to scan the radiographs only one time. The software performs all subsequent processing steps.