BACKGROUND: Low-intensity focused ultrasound (LIFU) has been shown to be a beneficial tool for autonomic nervous system modulation, but its effect on the left stellate ganglion (LSG) remains unknown. OBJECTIVE: To seek the effect of LIFU on myocardial infarction (MI)-induced LSG activation and ventricular arrhythmias (VAs). METHODS: In this study, 20 dogs were included and randomly divided into the LIFU (LIFU & MI, n = 8), Sham (sham LIFU & MI, n = 8), and Control group (sham LIFU & sham MI, n = 4). For each LIFU intervention (1.0-2.0 W, 10 minutes) of the LSG, the LSG function, ventricular effective refractory period (ERP), and temperature were tested pre-intervention and postintervention. Thereafter, MI was induced by left anterior artery ligation and VAs were recorded for 1 hour. At the end, both the LSG and the heart were extracted for biomedical and histological analysis. RESULTS: In the Sham group, no significant change was shown in ventricular ERP or LSG function for any intensity settings of sham LIFU intervention when compared with the group baseline. In the LIFU group, however, both 1.5 and 2.0 W LIFU modulation of LSG resulted in significant prolongation of ERP and attenuation of LSG function. Furthermore, the incidence of VAs was significantly attenuated in the LIFU group compared with the Sham group. Moreover, histological analysis showed that no damage or apoptosis was observed in LSG although a statistically significant increase was shown in temperature (maximal increase <1°C) with 1.5 and 2.0 W LIFU intervention. CONCLUSION: LIFU stimulation may be a safe and beneficial tool for LSG attenuation and VA prevention in the MI canine model.