INTRODUCTION: Growing evidence suggests that phosphodiesterase-5 inhibitors may mitigate ischemia-related renal damage through multiple mechanisms. We evaluated the role of tadalafil in renal function preservation during experimentally induced ischemia/reperfusion injury (IRI) in a solitary kidney porcine model. MATERIALS AND METHODS: Ten adult female pigs underwent left laparoscopic nephrectomy followed by a 1 week recovery period. They were then randomized to tadalafil versus no treatment prior to cross-clamping the contralateral renal hilum for 90 minutes. The experimental group received 40 mg tadalafil in two equally divided doses, 12 hours before and just prior to surgery. Serum creatinine for each animal was obtained just prior to ischemia induction (D0) and at days 1, 3 and 7 following hilar occlusion. Median creatinine at each time point was compared between groups using the Kruskal-Wallis test. RESULTS: Median serum creatinine at D0 was significantly lower in the tadalafil group (after two doses of tadalafil) (123.8 µmol/L versus 168.0 µmol/L, p = 0.009). As expected, median creatinine for each group rose significantly on D1 (p = 0.04 for each). Median creatinines following hilar occlusion at D1, D3 and D7, however, were not significantly different between groups. CONCLUSIONS: In this porcine model, administration of perioperative tadalafil improves preoperative renal function, but it does not appear to mitigate ischemia/ reperfusion injury from hilar occlusion.