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(1) Background: We aimed to compare the accuracy of after-hours CT reports created in a traditional in-house setting versus a teleradiology setting by assessing the discrepancy rates between preliminary and final reports. (2) Methods: We conducted a prospective study to determine the number and severity of discrepancies between preliminary and final reports for 7761 consecutive after-hours CT scans collected over a 21-month period. CT exams were performed during on-call hours and were proofread by an attending the next day. Discrepancies between preliminary and gold-standard reports were evaluated by two senior attending radiologists, and differences in rates were assessed for statistical significance. (3) Results: A total of 7209 reports were included in the analysis. Discrepancies occurred in 1215/7209 cases (17%). Among these, 433/7209 reports (6%) showed clinically important differences between the preliminary and final reports. A total of 335/5509 of them were in-house reports (6.1%), and 98/1700 were teleradiology reports (5.8%). The relative frequencies of report changes were not significantly higher in teleradiology. (4) Conclusions: The accuracy of teleradiology reports was not inferior to that of in-house reports, with very similar clinically important differences rates found in both reporting situations.