Objectives <p>To evaluate the safety and efficacy of transhepatic cardia-gastric fundus puncture (TCFP) for insufflation for CT-guided percutaneous gastrostomy (CPG).</p> Methods <p>The clinical data of 38 patients who underwent TCFP for insufflation and 161 patients who underwent percutaneous gastric body for insufflation at a single center were retrospectively analyzed. The operative time, success rate, complication rate, overall procedure time, and incidence of complications within 3&#xa0;months were collected.</p> Results <p>The success rate of insufflation was 100%, and no serious complications occurred during percutaneous gastric insufflation. The average time for insufflation via TCFP was 9.60 ± 6.62&#xa0;min, and that via gastric body puncture was 8.71 ± 71.8&#xa0;min, with no significant difference between the two (<i>p</i> = 0.485). The overall duration of gastrostomy in the TCFP group was 32.16 ± 10.27&#xa0;min and 33.94 ± 13.82&#xa0;min in the gastric body group, with no significant difference (<i>p</i> = 0.456). The incidence of submucosal air spread was 0% in the TCFP group and 9.9% in the gastric body group, with significant difference (<i>p</i> = 0.045). The complication rates following insufflation via TCFP and via gastric body puncture were 18.4% and 21.7%, respectively, with no significant difference between the two groups (p = 0.652). The perioperative pain score was 2 after insufflation via TCFP and via gastric body puncture, with no significant difference (<i>p</i> = 0.119). The overall mortality rate was 0 in the first postoperative month, with a 3-month mortality rate of 5% (10/199). The surviving patients showed a significant increase in weight from 51.81 ± 8.52&#xa0;kg to 52.52 ± 9.39&#xa0;kg at 3&#xa0;months postoperatively (<i>p</i> = 0.009).</p> Conclusions <p>TCFP for insufflation is safe and effective, with a 100% success rate and no increased risk of complications. The choice of procedure should be based on the patient's specific condition and the physician's experience.</p>