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OBJECTIVES To assess the effect of irrigation settings and the size of ureteral access sheath (UAS) on the maximal intra-pelvic pressure (IPPmax) during Ureteroscopy in pigs. MATERIAL AND METHODS In supine position, 3 anesthetized female pigs underwent cystoscopy to insert a 6F ureteral catheter in each ureter. Pigs were then turned to prone position to establish a percutaneous access, insert a 10F nephrostomy tube in the kidney, and connect it to a Urodynamic device. An 8F semi-rigid Ureteroscope or the Flex-X2 Flexible Ureteroscope were used with two irrigation settings; gravity flow and manual pumping using a commercial pump. Ureteroscopy was performed without UAS and with the UAS 9.5/11, 12/14, 14/16 at the uretero-pelvic junction and the IPPmax was recorded. RESULTS Under gravity irrigation, the recorded IPPmax during semi-rigid URS in the distal ureter and the renal-pelvis was 0, 30 cmH2O, respectively. Furthermore, the IPPmax during flexible URS in the renal-pelvis without UAS, with UAS 9.5/11.5, with UAS 12/14, with UAS 14/16 was 23, 6, 2, 1 cmH2O, respectively. Under manual pumping, the IPPmax during semi-rigid URs in the distal ureter and the renal-pelvis was 84, 105 cmH2O, respectively. Furthermore, the IPPmax during flexible URS in the renal-pelvis without UAS, with UAS 9.5/11.5, with UAS 12/14, with UAS 14/16 was 45, 46, 18, 1 cmH2O, respectively. CONCLUSION Manual pumping can significantly increase the IPPmax to unsafe levels during ureteroscopy. The UAS can significantly decrease the IPPmax, even under manual pumping. The larger the UAS, the lower the IPPmax. The use of UAS can render Ureteroscopy safer by acting as a safeguard against the consequences of increased IPP, even under forced irrigation.