Purpose: To study the effect of autonomic nervous system (ANS) dysfunction on glaucoma progression in patients with primary open angle glaucoma (POAG). Patients and Methods: A retrospective study of 40 cases of POAG patients who underwent regular reexamination for more than 3 years was performed. All participants were subjected to heart-rate variability (HRV) assessment. Patients were divided equally into the lowest and highest HRV groups according to the standard deviation value of the qualified normal to normal intervals (SDNN), a representative indicator of HRV. The lower the HRV, the more severe the ANS dysfunction with sympathetic predominance Visual field (VF) parameters and retinal nerve fiber layer (RNFL) thickness were used to evaluate and compare the progression of glaucoma damage between the two groups. Results: There were 20 cases in the lowest HRV group and 20 cases in the highest HRV group. The thinning rate of RNFL in the lowest HRV group was significantly faster than that in the highest HRV group (1.44 +/- 1.58 vs 0.29 +/- 0.56 mu m/year, P=0.00), accompanied by greater fluctuation of intraocular pressure (IOP) (P=0.04), lower diastolic blood pressure (P=0.01), mean blood pressure (P=0.04), and lower mean ocular perfusion pressure (P=0.04). Meanwhile, the incidence of central VF defects in the lowest HRV group was significantly higher than that in the highest HRV group (65.0% vs 30%, P=0.03). Linear regression analysis showed that there was a significant correlation between SDNN and the thickness loss rate of RNFL (P=0.01). Conclusion: POAG patients with lower HRV, which reflects ANS dysfunction with sympathetic predominance, presented faster glaucoma progression than patients with higher HRV. The more rapid progression of POAG with lower HRV may be explained by IOP and vascular risk factors.