Renal denervation (RDN) reduces renal efferent and afferent sympathetic activity thereby lowering blood pressure in resistant hypertension. The effect of modulation of the autonomic nervous system by RDN on atrial electrophysiology and ventricular rate control during atrial fibrillation (AF) is unknown. Here we report a reduction of ventricular heart rate in a patient with permanent AF undergoing RDN. Subsequently, we investigated the effect of RDN on AF-induced shortening of atrial effective refractory period, AF inducibility, and ventricular rate control during AF maintained by rapid atrial pacing in 12 pigs undergoing RDN (n=7) or sham procedure (n=5). During sinus rhythm, RDN reduced heart rate (RR-interval, 708±12 versus 577±19 ms; P=0.0021) and increased atrioventricular node conduction time (PQ-interval, 112±12 versus 88±9 ms; P=0.0001). Atrial tachypacing for 30 minutes increased AF inducibility and decreased AF cycle length. This was not influenced by RDN. RDN reduced ventricular rate during AF episodes by ≈24% (119±9 versus 158±19 bpm; P=0.0001). AF episodes were shorter after RDN compared with sham (12±3 versus 34±4 s; P=0.0091), but atrial effective refractory period was not modified by RDN. RDN reduced heart rate and reduced atrioventricular node conduction time during sinus rhythm and provided rate control during AF. AF-induced atrial electrical remodeling, AF inducibility, and AF cycle length were not modified, but duration of AF episodes was shorter after RDN. Modulation of the autonomic nervous system by RDN might provide rate control and reduce susceptibility to AF. Whether RDN may provide rate control in a larger number of patients with AF deserves further clinical studies.