This study evaluated the effects of propranolol on recovery of heart rate variability (HRV) after acute myocardial infarction and its relation to outcome in the Beta-blocker Heart Attack Trial (BHAT). Beta blockers improve mortality after acute myocardial infarction, but through an unknown mechanism. Depressed HRV, a measure of autonomic tone, predicts mortality after acute myocardial infarction. Whether beta blockers influence recovery of HRV after acute myocardial infarction, and thereby improve outcome, is unknown. We compared 24-hour HRV parameters at 1 week after acute myocardial infarction and after 6 weeks of treatment with propanolol (n = 88) or placebo (n = 96). The relation between 25-month outcome (death/acute myocardial infarction/congestive heart failure), propranolol treatment, and HRV was further analyzed. After 6 weeks, high-frequency (HF) power (log-normalized), an index of vagal tone, increased more in propranolol-treated patients (4.28 +/- 0.1 to 5.17 +/- 0.09 ms(2)) than in placebo-treated patients (4.26 +/- 0.09 to 4.77 +/- 0.1 ms(2), p <0.05). Sympathovagal balance measured by the low-frequency (LF) to HF ratio increased in placebo-treated patients (3.55 +/- 0.24 to 3.86 +/- 0.24) but decreased in those treated with propranolol (3.76 +/- 0.29 to 3.17 +/- 0.23, p <0.01). Other frequency-domain parameters increased over time but were not affected by propranolol. Propranolol blunted the morning increase in the LF/HF ratio. Recovery of HF, the strongest HRV predictor of outcome, and propranolol therapy independently predicted outcome. In summary, after acute myocardial infarction, propranolol therapy improves recovery of parasympathetic tone, which correlates with improved outcome, and decreases morning sympathetic predominance. These findings may elucidate the mechanisms by which beta blockers decrease mortality and reduce the early morning risk of sudden death after acute myocardial infarction.