BACKGROUND Low heart rate variability has been implicated as a risk factor for sudden death. However, no large epidemiological studies using sudden death as an outcome event have been reported. RESULTS A total of 6,693 consecutive patients who underwent 24-hour ambulatory ECG were followed up for 2 years; of these, 245 patients died suddenly. Clinical data at the time of 24-hour ambulatory ECG were collected for all patients who died suddenly and for a random sample of 268 patients from the study cohort. In all patients in sinus rhythm with or without occasional supraventricular arrhythmias at the 24-hour ECG (193 patients who died suddenly and 230 patients from the sample), heart rate variability parameters were derived. Patients with low short-term RR interval variability (mean during 24 hours of per-minute standard deviations [SD] of RR intervals < 25 msec) had a 4.1-fold higher risk (95% confidence interval [CI], 2.6, 8.1) for sudden death than patients with high short-term variability (> or = 40 msec); after adjustment for age, evidence of cardiac dysfunction, and history of myocardial infarction, the relative risk was 2.6 (95% CI, 1.4, 5.1). The crude relative risk of long-term RR interval variability (SD during 24 hours of per-minute means of RR intervals < 8 msec) was 4.4 (95% CI, 2.6, 7.7); after adjustment for the same risk factors, it was 2.2 (95% CI, 1.2, 4.1). Patients with a minimum heart rate > or = 65 beats per minute had a double risk of sudden death compared with those with a minimum heart rate < 65 beats per minute (adjusted relative risk, 2.1; 95% CI, 1.3, 3.6). CONCLUSIONS These findings support the theory that patients with low parasympathetic activity (low short-term RR interval variability) have an increased risk for sudden death independent of other risk factors.