Cardiovascular indices of pain are pervasive in the hospital setting. However, no research has examined the development of cardiac responses to acutely painful procedures in the first year of life. Our main goal was to synthesize evidence regarding the development of cardiovascular responses to acutely painful medical procedures over the first year of life in preterm and term born infants. A systematic search retrieved 6994 articles to review against inclusion criteria. A total of 41 studies were included in the review. In response to acutely painful procedures, most infants had an increase in mean heart rate (HR) that varied in magnitude both across and within gestational and postnatal ages. Research in the area of HR variability has been inconsistent, limiting conclusions. Accordingly, longitudinal research is needed to further understand the inherent variability of cardiovascular pain responses across and within gestational and postnatal ages, and the causes for the variability.