Evaluation of the efficacy and safety of chemical renal denervation by image-guided periarterial ethanol injection in pigs with emphasis on histopathological characteristics. Unilateral renal periarterial ethanol injection under general anesthesia was performed in 16 animals with the contralateral kidney serving as the control. All interventions were performed in an open MRI system under real-time multiplanar guidance. In 10 pigs an ethanol-carbostesin contrast agent mixture was injected with amounts of 5 ml (6 animals, group I) and 10 ml (4 animals, group II). 6 pigs (group III) were treated with 10 ml of an ethanol-polyacrylic (2 %) mixture. Four weeks after treatment, all animals underwent MRI including MRA. After euthanasia, macroscopic and histologic examination of the kidneys, renal arteries and periarterial tissue was performed to assess nerve injury and potential side effects. Furthermore, the norepinephrine concentration (RTNEC) in the renal tissue was determined as a surrogate parameter of efficacy. Histologic signs of nerval degeneration with various degrees of severity and circumferential distribution were found in all groups. Injury depths ranged up to 7.6 mm. In groups II and III the nerve count was significantly lower on the treated side. Renal artery stenosis was not observed in any pig. In all pigs of group II treatment resulted in neural degeneration with a mean RTNEC reduction of 53 % (p < 0.02). In groups I and III significant changes in RTNEC were not observed. Image-guided percutaneous periarterial ethanol injection was efficient and safe for renal denervation. The detected variations in histologic outcome underlined the importance of the preclinical optimization of the technique in order to maximize treatment effects in humans.· Renal denervation by percutaneous periarterial ethanol injection is an effective and potentially safe procedure.. · The percutaneous approach is less prone to anatomical and procedural limitations compared to catheter-based procedures.. · The achievable nerve injury depth lies beyond those of current RFA-probes.. · Efficacy depends on amount, concentration, viscosity and periarterial distribution of the ethanol-mixture.. · Establishing an optimal balance between these parameters is mandatory for a maximum treatment effect at minimum risk for sensitive adjacent structures..· Freyhardt P, Haage P, Walter A et al. Renal Sympathetic Denervation by Image-Guided Percutaneous Ethanol Injection - Histopathologic Characteristics, Efficacy and Safety. Fortschr Röntgenstr 2020; DOI: 10.1055/a-1085-2645.