Despite significant advances largely in surgical intervention, congenital heart disease (CHD) patients that survive past infancy often progress to develop advanced heart failure requiring specialized therapies. Although there are multiple modalities for the treatment of left ventricular heart failure, the mortality of right ventricular heart failure which is a common complication of patients with CHD has not been impacted. In addition to their physiologic differences, the left and right ventricles are derived from distinct progenitor pools thus adding to their fundamental molecular differences and impacting potential responses to therapies. Immediately after birth, there is a switch from fetal to adult circulation thus changing from two pumps acting in parallel to pumps performing in series due to decreased pulmonary arterial/right ventricle (RV) pressure. This is accompanied by metabolism switching from glycolytic to oxidative, contractile protein isoforms changing from fetal to adult and at the same time, cardiomyocytes losing proliferative capacity. To date, the comprehensive genetic analysis describing these specific transformations of the RV has not been defined in a large animal model. Using RNA-seq, we have generated gene expression data from the left and right ventricles of fetal (just prior to birth), 1 week old, and 1 month old male piglets to evaluate the gene expression changes that occur in the early postnatal period. Preliminary analysis of our data shows most of the changes in gene expression occur during the first week of birth and we have begun to uncover gene regulatory networks that are critical for postnatal RV remodeling. We are comparing the gene expression changes that occur postnatally in the pig to gene expression changes that occur during the corresponding time period in the mouse. A clearer understanding postnatal cardiac development in both small and large mammalian models will enhance understanding of the molecular and physiological differences of RV development and remodeling. These studies will provide a platform to exploit these newly identified pathways to develop novel treatment opportunities for CHD patients with RV failure.