In this study, we examined adults’ cardiac reactivity to repeated infant cry sounds in a genetically informative design. Three episodes of cry stimuli were presented to a sample of 184 adult twin pairs. Cardiac reactivity increased with each cry episode, indicating that subjects were increasingly sensitized to repeated infant distress signals. Non-parents showed more cardiac reactivity than parents, and males displayed a larger increase in heart rate (HR) in response to repeated cry sounds than females. Multivariate genetic modeling showed that the genetic component of adults’ HR while listening to infant crying was substantial. Genetic factors explained 37–51% of the variance in HR and similar genes influenced HR at baseline and HR reactivity to infant crying. The remaining variance in HR across the cry paradigm was accounted for by unique environmental influences (including measurement error). These results point to genetic and experiential effects on HR reactivity to infant crying that may contribute to the explanation of variance in sensitive and harsh parenting.