Background. In a previous study, we showed the feasibility of engineering conduit grafts made of swine small intestinal submucosa (SIS) with neonatal cardiac pericytes (CPs). Here, we report the results of a randomized, controlled, investigator-blinded trial assessing the safety and effectiveness of the new product for reconstructing the pulmonary artery (PA) in piglets. Methods and Results. Within trios of 4-week-old female littermate piglets, one was sacrificed to provide a source of CPs, while the other two were allowed to reach the age of 10 weeks. During this time interval, the donor CPs were culture-expanded, seeded onto SIS grafts, which were then shaped into conduits and conditioned in a flow bioreactor. Control unseeded SIS conduits were subjected to the same procedure. Then, recipient swine were randomized to surgical reconstruction of the left PA (LPA) with unseeded or CP-seeded SIS conduits. Doppler echocardiography and cardiac magnetic resonance imaging (CMRI) were performed at baseline and 4-months post-implantation. Vascular explants were examined using histology/immunohistochemistry. All animals completed the scheduled follow-up. No group difference was observed in baseline imaging data. The final Doppler assessment showed that the LPA’s blood flow velocity was similar in the treatment groups. CMRI revealed a mismatch in the average growth of the grafted LPA and contralateral branch in both treatment groups. Histology of explanted arteries demonstrated that the CP-seeded grafts had a thicker luminal cell layer, more intraparietal arterioles, and a higher expression of endothelial nitric oxide synthase (eNOS) compared with unseeded grafts. Moreover, the LPA stump adjacent to the seeded graft contained more elastin and less collagen than the unseeded control. Conclusions. Syngeneic CP engineering improves the in vivo luminal cellularization and intraparietal vascularization of SIS grafts and supports the elastic remodeling of the recipient artery.