Social interaction skill is important for psychological wellbeing, stress regulation, protection from disability and overall life satisfaction. Increase in activity of the vagus nerve, measured by heart rate variability (HRV), is associated with social interaction skill and decreased stress. In this meta-analysis we collated statistics from thirteen studies consisting of 787 participants who were participating in social interactions while HRV was simultaneously collected. Results revealed that while dyadic social interactions do not increase HRV generally from a baseline state, negative dyadic social interactions decrease HRV in a manner similar to the Trier Social Stress Task. Further, participants with psychopathology do not show cardiac autonomic flexibility during social interactions as indicated by reductions under stress and increases with subsequently positive social interactions. The role of age, gender and HRV index were also examined as potential moderators of HRV. Implications for health and wellbeing resulting from exposure to negative social interactions are discussed.