Transplant coronary artery vasculopathy (TCAV) following orthotopic heart transplantation (OHT) continues to be the primary reason for late graft failure in children. The current gold standard of diagnosis of TCAV is coronary angiography with or without intravascular ultrasound. This study investigates the longitudinal use of speckle-tracking echocardiographic strain imaging as an early non-invasive marker to screen for development of TCAV. Echocardiograms from patients who underwent OHT between 2006 and 2010 at Children’s Hospital Colorado (n = 50) were retrospectively assessed. Studies were evaluated at baseline (within a month of transplant), then at each annual clinical follow-up for peak longitudinal (LS) and circumferential (CS) strain, systolic strain rate, and diastolic strain rate using Siemens Velocity Vector Imaging software. Comparisons were made between subjects who did and did not develop TCAV. Mean time to TCAV diagnosis following OHT was 3.2 years (range 1–5.1 years). One year after transplant, significant differences were seen between groups in LS (non-TCAV mean −19.6%, TCAV mean −17.3%, p = 0.03) and longitudinal strain rate (non-TCAV mean −1.7%/s, TCAV mean −1.4%/s, p = 0.04). These differences persisted in subsequent years. Differences in LS preceded the catheterization-based diagnosis of TCAV in pediatric heart recipients and were noted as early as one year post transplant. Additionally, within-subject LS changes may have utility as a non-invasive screening tool to predict those patients at increased risk for development of TCAV.