To evaluate the improvement of radiologist performance in detecting bone metastases at follow up low-dose computed tomography (CT) by using a temporal subtraction (TS) technique based on an advanced nonrigid image registration algorithm.Twelve patients with bone metastases (males, 5; females, 7; mean age, 64.8 ± 7.6 years; range 51-81 years) and 12 control patients without bone metastases (males, 5; females, 7; mean age, 64.8 ± 7.6 years; 51-81 years) were included, who underwent initial and follow-up CT examinations between December 2005 and July 2016. Initial CT images were registered to follow-up CT images by the algorithm, and TS images were created. Three radiologists independently assessed the bone metastases with and without the TS images. The reader averaged jackknife alternative free-response receiver operating characteristics figure of merit was used to compare the diagnostic accuracy.The reader-averaged values of the jackknife alternative free-response receiver operating characteristics figures of merit (θ) significantly improved from 0.687 for the readout without TS and 0.803 for the readout with TS (P value = .031. F statistic = 5.24). The changes in the absolute value of CT attenuations in true-positive lesions were significantly larger than those in false-negative lesions (P < .001). Using TS, segment-based sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the readout with TS were 66.7%, 98.9%, 94.4%, 90.9%, and 94.8%, respectively.The TS images can significantly improve the radiologist's performance in the detection of bone metastases on low-dose and relatively thick-slice CT.