BACKGROUND To assess the technical feasibility and safety of trajectory image-guided percutaneous renal cryoablation in a porcine model. METHODS Six pigs (12 kidneys) were utilized. Only the posterior and lateral regions of the kidneys were considered. A bone-anchored dynamic reference frame (DRF) was inserted into the iliac crest and the O-Arm and StealthStation TREON System (OASSTS, Medtronic, CO, USA) was used to acquire 3-dimensional (3D) imaging of the kidneys. A hand-held pointing device was crafted from a cryoablation needle (Galil Medical, MN, USA) and an optical reference frame. The hand-held pointer/cryoablation needle ("cryoprobe") was then optically recognized by the OASSTS. The cryoprobe was then used to navigate its tip into a randomly chosen renal region of interest using 3D trajectory images. Two freeze-thaw cryoablation cycles were then performed. We assessed treatment times and effective radiation doses. We also assessed concordance between projected iceball location on trajectory imaging and cryolesion location on necropsy. RESULTS The mean total treatment time was 24.0 minutes. The mean effective radiation dose was 23.7 mSv per kidney treated. The trajectory-guided images used to place the cryoprobe tips into the renal region of interest agreed with the necropsy-determined location of the cryolesion in all cases. Injury to a lumbar muscle and a renal pelvis were observed in two separate cases, respectively. CONCLUSIONS Trajectory image-guided percutaneous renal cryoablation using OASSTS is technically feasible, appears safe, and is associated with acceptable levels of radiation exposure. Comparison of trajectory image-guidance and cryolesions on necropsy demonstrated concordant needle placement.