Heart failure is characterized by the loss of sympathetic innervation to the ventricles, contributing to impaired cardiac function and arrhythmogenesis. We hypothesized that renal denervation (RDx) would reverse this loss. Male Wistar rats underwent myocardial infarction (MI) or sham surgery and progressed into heart failure for four weeks before receiving bilateral RDx or sham RDx. After a further three weeks, left ventricular (LV) function was assessed and ventricular sympathetic nerve fibre density determined via histology. Post-MI heart failure rats displayed significant reductions in ventricular sympathetic innervation and tissue noradrenaline content (nerve fibre density in the LV of MI+sham RDx hearts was 0.31 ± 0.05 % vs. 1.00 ± 0.10 % in sham MI+sham RDx group, P < 0.05) and RDx significantly increased ventricular sympathetic innervation (0.76 ± 0.14 %, P < 0.05) and tissue noradrenaline content. MI was associated with an increase in fibrosis of the non-infarcted ventricular myocardium which was attenuated by RDx. RDx improved LV ejection fraction and end-systolic and -diastolic areas when compared to pre-RDx levels. This is the first study to show an interaction between renal nerve activity and cardiac sympathetic nerve innervation in heart failure. Our findings show denervating the renal nerves improves cardiac sympathetic innervation and function in the post-MI failing heart.