OBJECTIVE: High levels of high-frequency heart rate variability (HF-HRV), related to parasympathetic-nervous-system functioning, have been associated with longer survival in patients with myocardial infarction and acute trauma and in patients undergoing palliative care. From animal studies linking higher vagal activity with better immune system functioning and reduced metastases, we hypothesized that higher HF-HRV would predict longer survival in patients with metastatic or recurrent breast cancer (MRBC). METHODS: Eighty-seven patients with MRBC participated in a laboratory task including a 5-minute resting baseline electrocardiogram. HF-HRV was computed as the natural logarithm of the summed power spectral density of R-R intervals (0.15-0.50 Hz). In this secondary analysis of a study testing whether diurnal cortisol slope predicted survival, we tested the association between resting baseline HF-HRV on survival using Cox proportional hazards models. RESULTS: A total of 50 patients died during a median follow-up of 7.99 years. Higher baseline HF-HRV predicted significantly longer survival, with a hazard ratio of 0.75 (95% confidence interval = 0.60-0.92, p = .006). Visceral metastasis status and baseline heart rate were related to both HF-HRV and survival. However, a combination of HF-HRV and heart rate further improved survival prediction, with a hazard ratio of 0.64 (95% confidence interval = 0.48-0.85, p = .002). CONCLUSIONS: Vagal activity of patients with MRBC strongly predicted their survival, extending the known predictive window of HF-HRV in cancer beyond palliative care. Vagal activity can be altered by behavioral, pharmacological, and surgical interventions and may be a promising target for extending life expectancy in patients with metastasizing cancer.