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To assess whether temporal subtraction (TS) images of brain CT improve the detection of suspected brain infarctions. Study protocols were approved by our institutional review board, and informed consent was waived because of the retrospective nature of this study. Forty-two sets of brain CT images of 41 patients, each consisting of a pair of brain CT images scanned at two time points (previous and current) between January 2011 and November 2016, were collected for an observer performance study. The 42 sets consisted of 23 cases with a total of 77 newly developed brain infarcts or hyperdense artery signs confirmed by two radiologists who referred to additional clinical information and 19 negative control cases. To create TS images, the previous images were registered to the current images by partly using a non-rigid registration algorithm and then subtracted. Fourteen radiologists independently interpreted the images to identify the lesions with and without TS images with an interval of over 4 weeks. A figure of merit (FOM) was calculated along with the jackknife alternative free-response receiver-operating characteristic analysis. Sensitivity, number of false positives per case (FPC) and reading time were analyzed by the Wilcoxon signed-rank test. The mean FOM increased from 0.528 to 0.737 with TS images (p < 0.0001). The mean sensitivity and FPC improved from 26.5% and 0.243 to 56.0% and 0.153 (p < 0.0001 and p = 0.239), respectively. The mean reading time was 173 s without TS and 170 s with TS (p = 0.925). The detectability of suspected brain infarctions was significantly improved with TS CT images. • Although it is established that MRI is superior to CT in the detection of strokes, the first choice of modality for suspected stroke patients is often CT. • An observer performance study with 14 radiologists was performed to evaluate whether temporal subtraction images derived from a non-rigid transformation algorithm can significantly improve the detectability of newly developed brain infarcts on CT. • Temporal subtraction images were shown to significantly improve the detectability of newly developed brain infarcts on CT.