Objective To calculate the success rate of pterygopalatine ganglion puncture via the frontozygomatic angle approach by CT scans, and to analyze the anatomical factors affecting the success of puncture. Methods The pterygopalatine ganglions under the MRI images of 6 patients and the relevant bone markers were identified, then skull specimens were punctured to observe the factors that influencing the success rate. Finally, the puncture was simulated in the CT images of 142 patients (284 sides). The success of the puncture was recorded and the influencing factors were observed and analyzed. Results: The success rate of the pterygopalatine ganglion puncture via the frontozygomatic angle approach in the cranial specimens was 14/20, and that in the CT imaging was 53.9%. The influencing factors are mainly the enlarged sphenoidal spine, stenotic pterygomaxillary fissure and the posterior-superior displacement of the frontozygomatic angle. Conclusion: The sphenoidal spine and the width pterygomaxillary fissure may affect the pterygopalatine ganglion puncture via the frontozygomatic angle. Imaging examination before puncture may provide valuable information for clinical selection of puncture pathway.