Because decreased heart rate variability measured after an acute myocardial infarction (AMI) has been demonstrated to predict subsequent mortality and sudden death, and an efficacy analysis of the Danish Verapamil Infarction Trial II (DAVIT II) demonstrated that long-term postinfarction treatment with verapamil significantly reduced sudden death, the aim of the present substudy was to evaluate the effect of verapamil on heart-rate variability in the time and frequency domain, measured in two 5-minute segments during the day and night. Thirty-eight patients were examined by Holter monitoring, at 1 week, that is, before randomization, and at 1 month after infarction; 22 of the patients were examined 12-16 months after infarction as well. In both treatment groups (verapamil and placebo) no significant alteration of heart rate variability during the day-time was demonstrated from before to after 1 and 12-16 months of treatment. In accord with the known reduction of overall heart rate by verapamil, a significant increase of mean NN interval from before to after 1 (P = 0.0004) and 12-16 months (P = 0.004) of treatment was seen in the verapamil, but not in the placebo, group at night. Parameters generally interpreted as an index of parasympathetic modulation, that is, RMSSD, pNN50, and high-frequency power, increased significantly at 1 month (P = 0.04, P = 0.03, NS, respectively) and 12-16 months (P = 0.03, P = 0.04, P < 0.05) after AMI in the verapamil, but not in the placebo, group. In conclusion, the present study indicates that verapamil shifts the autonomic balance to a vagal preponderance or sympathetic attenuation in the postinfarction period.