Objectives: To compare helium and carbon dioxide gas insufflation for the creation of pneumocystis during bladder cryoablation in an effort to optimize the technique. Methods: Nine pigs were divided into 3 groups. The pigs in groups 1, 2, and 3 underwent bladder cryoablation in a normal saline, carbon dioxide gas, and helium gas environment, respectively. Each group underwent 2 freeze-thaw cycles of the bladder dome. The bladder pressure measurements were recorded every 5 seconds throughout the cryoablation procedure. Bladder integrity was evaluated with both cystoscopic and laparoscopic visualization. All pigs were killed at the completion of the procedure, and the bladders were harvested for histopathologic evaluation. Results: All 9 pigs successfully underwent bladder wall cryoablation. Bladder integrity was maintained in all 6 pigs in groups 1 and 3. In group 2, 2 bladder ruptures were documented. All group 2 pigs had a significantly increased bladder pressure during the 2 thaw cycles of the cryoablation procedure, with the peak pressure >70-100 mm Hg before venting of the excess carbon dioxide gas. No intervention was required to stabilize the bladder pressure in groups 1 and 3. The average change in pressure per 5-second interval during both thaw cycles for groups 1, 2, and 3 was 0.16, 6.96, and 0.42 mm Hg/s, respectively (P = .0003). Group 3 showed mild hemorrhage on histologic examination. Conclusions: The creation of pneumocystis with helium gas reduces sublimation and eliminates the problems of rapidly fluctuating bladder pressures and decreased visibility previously noted with carbon dioxide gas during bladder cryoablation.