BACKGROUND AND PURPOSE: Poststroke prognosis is associated with autonomic status. The purpose of our study was to determine whether percutaneous mastoid electrical stimulator (PMES) can alleviate abnormal heart rate variability (HRV) and improve clinical outcome. METHODS: This prospective, randomized, double-blinded, placebo-controlled study enrolled a total of 140 patients with autonomic dysfunction within 3d after acute ischemic stroke. The patients were treated with PMES or sham stimulation once daily over a period of 2 weeks. HRV was primarily assessed by the fractal dimension (FD) at admission and 2 weeks. All patients were followed up for 3 months. The clinical outcome was death and major disability (modified Rankin Scale score>/= 3) at 3 months after acute ischemic stroke. RESULTS: FD of the 2-week treatment period increased in PMES groups. PMES can significantly alleviate abnormal HRV. The difference in FD of the 2-week treatment period between the PMES and sham groups was significant (1.14 +/- 0.27 vs. 1.00 +/- 0.23; P = 0.001). In fully adjusted models, PMES was associated with reduced 3-month mortality (adjusted odds ratio, 0.32; 95% confidence interval, 0.11-0.93; P = 0.036). No significant group differences were seen in three major disability and composite outcome (P > 0.05). CONCLUSIONS: PMES was a safe, effective, and low-cost therapy to alleviate HRV and could significantly reduce mortality in the early recovery phase after acute ischemic stroke.