Hyperuricemia has been associated with low heart rate variability (HRV), however whether there is an association between uric acid (UA) and HRV changes after hemodialysis (HD) is unknown. The aim of this study was to investigate the role of UA in HRV changes before and after HD in non-diabetic patients. Ninety-six non-diabetic patients under maintenance HD were enrolled. HRV was examined to assess changes before and after HD. A change in HRV (DeltaHRV) was calculated as post-HD HRV minus pre-HD HRV. Compared to the patients with a UA level <== 7 mg/dL, those with a UA level > 7 mg/dL had lower 鈭唄igh frequency (HF)% (p = 0.027). UA was negatively associated with 鈭咹F% (r = -0.247, p = 0.015) and 鈭唋ow frequency (LF)/HF (r = -0.236, p = 0.021) in the non-diabetic patients undergoing HD. Furthermore, in multivariate analysis after adjustments for demographic, clinical, and biochemical characteristics and medications, UA was independently associated with 鈭咹F% (per 1 mg/dL, unstandardized coefficient beta = -2.892; 95% CI, -5.066 to -0.717; p = 0.010) and 鈭哃F/HF (per 1 mg/dL, unstandardized coefficient beta = -0.165; 95% CI, -0.291 to -0.038; p = 0.011). Hyperuricemia contributed to lesser HF% and LF/HF increase after HD in the non-diabetic patients, reflecting a state of impaired sympatho-vagal equilibrium in non-diabetic HD patients with hyperuricemia. Lowering UA levels may have the potential to improve increased HRV in non-diabetic HD patients.