To investigate the influence of a cone-beam CT (CBCT) based Virtual Injection software on patient radiation exposure during prostate artery embolization (PAE). All consecutive patients from January 2019 to May 2022 treated with PAE using CBCT at a single institution were retrospectively analyzed. Radiation exposure (Total Air Kerma (AK), Peak Skin Dose (PSD)), fluoroscopy time (FT) and operation time were recorded. The influence of age, body mass index (BMI), radial access and use of Virtual Injection software (Embo ASSIST, GE Healthcare, Chicago, IL) were assessed. A total of 131 patients had PAE with CBCT, of whom 77 patients (77/131;58.8%) using Virtual Injection software and 40 (40/131;30.5%) using radial access. Radial access and Virtual Injection both significantly reduced AK, PSD and FT with respectively (601 ± 503 vs. 962 ± 593 mGy, P = 0.01) and (642 ± 451 vs. 1150 ± 637 mGy, P = 0.01); (295 ± 243 vs. 683 ± 476 mGy, P< 0.001) and (358 ± 251 vs. 860 ± 510 mGy, P = 0.001); (33 ± 15.3 vs. 43,1 ± 18.6 min, P = 0.004) and (35.6 ± 15.4 vs. 46.6 ± 20 min, P = 0.001). Virtual Injection use also significantly reduced operation time (94.6 ± 41.3 min vs. 115.2 ± 39.6, P = 0.005). In multivariate analysis, AK and PSD reduction were associated with lower patient BMI, shorter FT and Virtual Injection use. FT and operation time reduction were associated with Virtual Injection use. The use of Virtual Injection software in PAE planning and guidance is associated with reduced radiation exposure and operative time.