<h3>Purpose</h3> Intravascular ultrasound (IVUS) provides unique prognostic information on allograft vasculopathy progression by detecting increase in maximal intimal thickness (MIT) during the first post-heart transplant (HT) year. Later changes in coronary morphology, their prognostic relevance, and risk factors are however unexplored. <h3>Methods and Materials</h3> We investigated whether changes in coronary morphology assessed in patients receiving serial IVUS at 1 and 5 years after HT predicted fatal and non-fatal cardiovascular (CV) events. We additionally analyzed the impact of metabolic risk factors on changes in IVUS measurements. <h3>Results</h3> 107 consecutive patients receiving HT between 1999 and 2007 entered the study. During the 11 years of follow-up, incidence of CV death was 8±3% and of CV events was 26±6%. Between year 1 and 5, MIT and intimal volume increased, lumen volume decreased (P<0.001 for all), while vessel volume was unchanged. By Cox's model, only MIT increase was associated with subsequent CV death (RR=4.2 [1.2-12.1] per mm, P=0.03) and CV events (RR=2.6 [1.1-5.6] per mm; P=0.03). By ROC curves, we found that a MIT change cut-off of 0.35mm best identified patients at risk for CV death and events (Figure). Among the metabolic parameters, increasing triglycerides and HDL-cholesterol ≤65mg/dl predicted MIT increase ≥ 0.35mm (P≤0.05). <h3>Conclusions</h3> This study provides the first suggestive evidence that MIT increase represent a relevant prognostic marker also after the first year after HT. In addition, the finding that clinically relevant MIT is predicted by lipid pattern typical of insulin resistance, provide a strong rationale supporting aggressive therapeutic interventions against metabolic abnormalities mid and long-term after HT.