To evaluate application of a computed tomography (CT)-ultrasound fusion imaging technique to unilateral percutaneous vertebroplasty (PVP) for treating patients with osteoporotic thoracolumbar compression fracture. Fourteen patients with osteoporotic thoracolumbar compression fractures were included, randomly divided into CT-ultrasound fusion imaging (n = 7) and traditional X-ray fluoroscopy groups (n = 7). Patients in the first group underwent unilateral PVP using real-time CT-ultrasound fusion imaging. A body surface locator was placed on the side contralateral to the scheduled puncture site (2-3 cm from the spinous process). Patient CT image information was recorded in the ultrasound system for registration during real-time ultrasound and CT fusion imaging, and one-click automatic registration was then performed. The puncture point and target point at which the puncture needle arrived were determined on CT images, with the puncture being performed under ultrasound guidance. Patients in the second group underwent X-ray fluoroscopy-guided PVP. Bone cement injection was injected under monitoring using a C-arm X-ray system. Patients' X-ray exposure and puncture times were recorded and compared between the two groups. The average puncture times in the CT-ultrasound fusion imaging and traditional X-ray fluoroscopy groups were 2.50±0.31 min (without exposing patients and operators to radiation) and 5.00±0.65 min (with the same duration of radiation exposure), respectively. The average times for bone cement injection were 3.29±0.81 min and 3.50±0.86 min, respectively. The mean visual analog scale (VAS) scores were 2.10±0.11 and 2.20±0.21, respectively. The bone cement was evenly distributed without cement leakage in patients in the CT-ultrasound fusion imaging group, but a poor distribution of bone cement and bone cement leakage were found in one patient in the traditional X-ray fluoroscopy group. Real-time CT-ultrasound fusion imaging is easy to perform, and provides precise localization of the puncture point, path, and target point. The selected puncture path was reasonable, and the needle had reached the target point accurately, which increased the success rate of puncture without radiation exposure.