Low systemic blood flow occurs in up to 30% of infants born at less than 30 wk gestation. It is associated with increased morbidity and mortality, and current treatments are ineffective in 40% of cases. The aim of this study was to assess the ability of the preterm heart to respond to the acute shifts in preload and afterload that occur at the time of birth. Myocardial and coronary vascular function was assessed using an isolated working heart model in term (115 days) and preterm (92 days) piglets. Cardiac output/kg body wt in preterm hearts was ~50% lower than that of term hearts (P = 0.001). Pressure development was similar in term and preterm hearts. Elevations in preload increased cardiac output and aortic flow similarly in term and preterm hearts, demonstrating significant preload "reserve". By contrast, elevations in afterload markedly depressed aortic flow, with a greater proportion of cardiac output being distributed to coronary flow in preterm hearts at high afterloads. The demands of increased workload were associated with greater increases in coronary flow in preterm hearts compared with term hearts. In preterm hearts, exposure to maternal glucocorticoids resulted in increased aortic flow when afterload was below 25 mmHg. These data suggest the preterm heart lacks the functional capacity to acutely adapt to postnatal afterload. To maximize systemic blood flow in preterm infants, treatments limiting afterload, while harnessing significant preload reserve, should be further explored.