The aim of this study was to examine whether signs of neurotoxic influence on the autonomic nervous system, after lengthy occupational lead exposure, could be revealed by appropriate cardiac rhythm analysis. A total of 109 male lead-exposed workers and 27 controls were examined in a cross-sectional study. In addition, 17 lead-exposed participants were investigated a second time in a follow-up study 4 years later. Heart rate variability was assessed in rest, strain, and recovery phases. In the cross-sectional study, lead-exposed persons showed a delayed restoration of cardiac rhythm parameters to the initial vegetative state after the strain phase. This effect significantly increased over a period of 4 more years of exposure in the 17 workers participating in the follow-up study. We found vagal depression caused by long-term lead exposure within the current threshold limit value range, which can be interpreted as an adverse effect.