Ureteral stents are routinely used in daily urological practice and it is widely recognized that it can produce significant symptoms like infection encrustation, patient discomfort. Several biodegradable stents have been reported but all of them have failed. The main challenge remains to have a homogenous degradation preventing the formation of fragments that can cause obstruction. We recently described biodegradable ureteral stent (BUS) produced with natural-based polymers. In the present study, we assessed in-vivo (porcine model) this newly developed BUS, by comparing its degradation mechanical properties drainage physiological and histological features with those of a commercially available ureteral stent. To perform an in-vivo assessment of a newly developed BUS produced with natural-based polymers. The BUS is based on a patented technology combining the injection process with the use of supercritical fluid technology. A study was conducted with a total of 10 domestic pigs were used. In 7 animals the experimental BUS stent was inserted, whereas in the remaining a commercially available stent was used. Post-stenting intravenous pyelogram was used to evaluate the degree of hydronephrosis. The in-vivo stent degradation was measured as a function of weight loss. Moreover, the tensile properties of the BUS were tested during in vivo degradation. After a maximum of 10 days, animals were sacrificed and necropsy was performed. Tissues were compared between the stented groups as well as between the non-stented contralateral ureters and stented ureters in each group. Biocompatibility was assessed by histopathological grading. In all cases, the BUS was only visible during the first 24 hours on X-ray, and in all cases, the BUS was completely degraded in urine after 10 days, as confirmed on necropsy. During the degradation process, the mechanical properties of the BUS decreased, while the commercial ureteral stents remained constant. At all time-points after stent insertion, the level of hydronephrosis was minimal. Overall, animals stented with BUS had an average grade of hydronephrosis which was lower compared to the controls. The BUS showed better pathological conditions, and hence better biocompatibility when compared with commercial stents. Notwithstanding the limitations of the present study, the in vivo testing of our novel natural origin polymer-based BUS suggests this device to feature homogeneous degradation, good urine drainage, and high biocompatibility.