The main intervention for coronary artery disease is stent implantation. We aim to predict post-intervention target lesion failure (TLF) months before its onset, an extremely challenging task in clinics. This post-intervention decision support tool helps physicians to identify at-risk patients much earlier and to inform their follow-up care. We developed a novel machine-learning model with three components: a TLF predictor at discharge via a combination of nine conventional models and a super-learner, a risk score predictor for time-to-TLF, and an update function to manage the size of the at-risk cohort. We collected data in a prospective study from 120 medical centers in over 25 countries. All 1975 patients were enrolled during Phase I (2016–2020) and were followed up for five years post-intervention. During Phase I, 151 patients (7.6%) developed TLF, which we used for training. Additionally, 12 patients developed TLF after Phase I (right-censored). Our algorithm successfully classifies 1635 patients as not at risk (TNR = 90.23%) and predicts TLF for 86 patients (TPR = 52.76%), outperforming its training by identifying 33% of the right-censored patients. We also compare our model against five state of the art models, outperforming them all. Our prediction tool is able to optimize for both achieving higher sensitivity and maintaining a reasonable size for the at-risk cohort over time.