We assessed whether pravastatin attenuates cardiac sympathetic reinnervation after myocardial infarction through activation of ATP-sensitive potassium (K_ATP) channels. Epidemiological studies showed that men treated with statins appear to have a lower incidence of sudden death than men without statins. However, the specific factor for this remained disappointingly elusive. Twenty-four hours after ligation of the anterior descending artery, male Wistar rats were randomized to either vehicle, nicorandil (a specific mitochondrial K_ATP channel agonist), pinacidil (a nonspecific K_ATP channel agonist), pravastatin, glibenclamide (a K_ATP channel blocker), or a combination of nicorandil and glibenclamide, pinacidil and glibenclamide or pravastatin and glibenclamide for 4 weeks. Myocardial norepinephrine levels revealed a significant elevation in vehicle-treated rats at the remote zone compared with sham-operated rats (2.54 ± 0.17 vs. 1.26 ± 0.36 µg/g protein, P < 0.0001), consistent with excessive sympathetic reinnervation after infarction. Immunohistochemical analysis for tyrosine hydroxylase, growth associated factor 43 and neurofilament also confirmed the change of myocardial norepinephrine. This was paralleled by a significant upregulation of tyrosine hydroxylase protein expression and mRNA in the vehicle-treated rats, which reduced after administering either nicorandil, pinacidil or pravastatin. Arrhythmic scores during programmed stimulation in the vehicle-treated rats were significantly higher than those treated with pravastatin. In contrast, the beneficial effects of pravastatin-induced were reversed by the addition of glibenclamide, implicating K_ATP channels as the relevant target. The sympathetic reinnervation after infarction is modulated by activation of K_ATP channels. Chronic use of pravastatin after infarction, resulting in attenuated sympathetic reinnervation by activation of K_ATP channels, may modify the arrhythomogenic response to programmed electrical stimulation.