Introduction: Autonomic nervous system (ANS) function quantified by heart rate variability (HRV) was associated with long-term prognosis, but it was rarely used in the evaluation of patients with heart failure, especially those with cardiac resynchronization therapy-defibrillator (CRT-D) implantation. This study aimed to describe the changes in ANS function among patients who underwent CRT-D with remote home monitoring function, and explore predictive value of HRV for ventricular tachyarrhythmias (VTAs) and all-cause mortality. Method: Patients who underwent CRT-D implantation were included. Device-measured all-day HR, night-time HR, and HRV (measured by the standard deviation of the atrial-atrial sensed intervals) were used to quantify ANS function. Multivariate Cox proportional hazards models were fitted to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of VTAs or all-cause mortality in relation to ANS function at baseline and 6 months post-implantation. The cutoff value was determined using restrictive cubic splines. Multivariable logistic regression was further established to determine factors influencing postoperative HRV. Results: A total of 170 patients treated with CRT-D were eligible for analysis. During a median follow-up period of 50.8 months, 61 patients died and 69 patients experienced at least one spontaneous episode of VTAs. At 6 months after CRT implantation, 114 patients showed improvement in HRV, increasing from 66.4 +/- 19.4 ms to 76.7 +/- 21.2 ms. The postoperative HRV was associated with both all-cause mortality (HRs: 0.983; 95% CI: 0.968 to 0.998, p = 0.012) and VTAs (HRs: 0.973; 95% CI: 0.954 to 0.993, p = 0.008), and the relative risk would significantly increase when the postoperative HRV lower than 75 ms. After adjusting for basic ANS function and possible influencing factors, patients without diabetes (p = 0.018) and with higher daily physical activity (p = 0.041) could maintain higher postoperative HRV after CRT implantation. Conclusion: More than two-thirds of heart failure patients showed improvement in ANS function following CRT treatment. However, patients with diabetes and low daily physical activity levels have difficulty maintaining a higher postoperative HRV, which is associated with a worse clinical outcome.