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Objective To evaluate accuracy of fracture detection and therapeutic impact of a single-shot CT protocol as a primary imaging tool in all patients with clinical suspicion of wrist injury, and evaluate the resulting impact on therapy. Materials and methods We performed a single-institution study on all patients with suspicion of fractures of the wrist and carpus. All patients underwent conventional radiography, thereafter single-shot wrist CT, and then 1-year follow-up. Physicians and radiologists prospectively scored likelihood of fracture presence on a five-point scale before and after CT. Three surgeons proposed a treatment regimen (functional, cast, reduction, or operative) based on clinical and radiological data, first with knowledge of conventional radiography, and then with knowledge of CT. The reference standard for fracture presence was based on all data. We performed receiver operating characteristic (ROC) analyses and calculated proportion of wrists with treatment changes due to CT imaging. Results Ninety-eight patients participated (63% female, mean age 53, range, 18–87 years old) with 100 wrist CTs. Conventional radiography detected true-positive fractures in 45, and CT in 61 wrists. The areas under the curve for fracture detection were 0.85 (95% CI 0.77–0.93) for conventional radiography and 0.97 (95% CI 0.93–1.00) for CT. Treatment changed in 24 (24%, 95% CI 16–33%) - 31 (31%, 95% CI 23–41%) wrists, mostly involving a decrease in the rate of cast immobilization. Conclusions Single-shot CT in patients with clinical suspicion of wrist injury increases accuracy of fracture detection. This has a significant impact therapy in this population, mainly on cast immobilization. Trial Registration We registered the study at www.clinicaltrials.gov, NL43482.091.13.