Background: Myocardial blood flow (MBF) quantification by Rubidium-82 positron emission tomography (PET) has shown promise for cardiac allograft vasculopathy (CAV) surveillance and risk stratification post heart transplantation. The objective was to determine the prognostic value of serial PET performed early post transplantation., Methods and Result: Heart transplant (HT) recipients at the University of Ottawa Heart Institute with 2 PET examinations (PET1 = baseline, PET2 = follow-up) within 6 years of transplant were included in the study. Evaluation of PET flow quantification included stress MBF, coronary vascular resistance (CVR), and myocardial flow reserve (MFR). The primary composite outcome was all-cause death, re-transplant, myocardial infarction, revascularization, allograft dysfunction, cardiac allograft vasculopathy (CAV), or heart failure hospitalization. A total of 121 patients were evaluated (79% male, mean age 56 ± 11 years) with consecutive scans performed at mean 1.4 ± 0.7 and 2.6 ± 1.0 years post HT for PET1 and PET2, respectively. Over a mean follow-up of 3.0 (IQR 1.8, 4.6) years, 26 (22%) patients developed the primary outcome: 1 death, 11 new or progressive angiographic CAV, 2 percutaneous coronary interventions, 12 allograft dysfunction. Unadjusted Cox analysis showed a significant reduction in event-free survival in patients with PET1 stress MBF < 2.1 (HR: 2.43, 95% CI 1.11-5.29 P = 0.047) and persistent abnormal PET1 to PET2 CVR > 76 (HR: 2.19, 95% CI 0.87-5.51 P = 0.045). There was no association between MFR and outcomes., Conclusion: Low-stress MBF and persistent increased CVR on serial PET imaging early post HT are associated with adverse cardiovascular outcomes. Early post-transplant and longitudinal assessment by PET may identify at-risk patients for increased surveillance post HT., (© 2020. American Society of Nuclear Cardiology.)