OBJECTIVE To improve early detection of disease in chest radiographs, the authors developed a digital processing technique that geometrically warps and subtracts a previous radiograph from a current radiograph to produce a temporal subtraction image. An observer test was performed to evaluate the effects of the temporal subtraction image technique on detection of interval change. METHODS Fifty pairs of chest radiographs, including a baseline examination and a subsequent radiograph, were selected (25 cases in which potentially important new abnormalities had developed, and 25 in which there was no interval change). The baseline examination was chosen from multiple prior radiographs to minimize initial misregistration. By means of receiver operating characteristic (ROC) analysis, the ability of 11 observers to detect pathologic change when viewing the paired digitized baseline and subsequent radiographs was compared with their ability when viewing the same paired radiographs together with temporal subtraction images. Positive cases demonstrated focal new abnormalities that were greater than 1 cm in diameter. RESULTS The mean area (Az) under the ROC curves increased from 0.89 without to 0.98 with the temporal subtraction images. When the paired digitized previous and current chest radiographs were viewed in conjunction with the temporal subtraction images, a significant improvement in detection of new abnormalities was achieved (P = .00004), whereas the mean interpretation time was reduced by 19.3% (from 52 to 42 seconds, including the time to record the score and to move to the next case) (P = .0019). CONCLUSIONS The temporal subtraction technique can significantly improve sensitivity and specificity for detection of interval change in chest radiographs.