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Previous studies have suggested that angiographically detected persistent contrast staining (PSS) at follow-up may predict subsequent very late stent thrombosis. The Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial was a dual-arm, factorial, randomized trial in patients with ST-segment elevation myocardial infarctions. All follow-up angiograms (1,330 lesions in 1,115 patients, median time 13.3 months) without major cardiovascular events before follow-up angiography were analyzed at a core laboratory blinded to clinical events for the presence of PSS (defined as contrast staining outside the stent contour extending to ≥20% of the stent diameter). Corresponding follow-up intravascular ultrasound (IVUS) data (275 lesions in 248 patients) were also evaluated to assess the mechanisms of PSS. PSS was present in 23 patients (2.1%) at follow-up and was not more common with paclitaxel-eluting than with bare-metal stents. All 6 PSS patients with follow-up IVUS had stent malapposition (vs 41.2% malapposition in the follow-up IVUS cohort). Comparing poststent and follow-up IVUS, 2 patients had late acquired and 4 had persistent malapposition; all 6 showed positive vessel remodeling from baseline to follow-up (mean vessel area 22.0 ± 8.0 to 32.4 ± 11.7 mm(2), p = 0.07). During 3-year follow-up, stent thrombosis developed in no patient with PSS compared with 8 PSS-negative patients (0% vs 0.8%, p = 0.68). The rates of revascularization and major adverse cardiovascular events were also not increased in PSS patients. In conclusion, in the large-scale HORIZONS-AMI trial, PSS at angiographic follow-up was infrequent and was associated with late stent malapposition and positive remodeling but was independent of stent type. Identification of PSS was not associated with subsequent stent thrombosis., (Copyright © 2013 Elsevier Inc. All rights reserved.)