Objective. High intraluminal pressure during ureterorenoscopy (URS) increases risk of infectious and haemorrhagic complications. Intrarenal pressure may be reduced by the use of ureteral access sheaths (UASs), which on the other hand may cause ureteral damage. We have previously shown that the β-agonist isoproterenol (ISO), when administered topically in the irrigation fluid, is able to inhibit ureteral muscle tone and lower intrarenal pressure during URS. The aim of this study was to examine the effect of ISO on the success rate of UAS insertion in a porcine model. Materials and Methods. 22 pigs in which a UAS could not initially be placed were randomized to endoluminal irrigation with either ISO (0.1 μg/mL) or saline before a new insertion trial. Subsequently, it was registered whether the UAS could be passed without resistance. During extraction of the sheath, any ureteral lesions were characterized ureteroscopically using the PULS classification system. Surgeons were blinded to randomization. Results. In the ISO group, the observed effect of irrigation was 63% successful UAS insertions, compared to 27% in the saline group. No serious lesions (<PULS grade 2) were observed in the ISO group. Conclusions. Endoluminal irrigation with ISO may facilitate UAS insertion and potentially decrease UAS related ureteral lesions.