HORIZONS-AMI was a prospective dual-arm randomized trial of different antithrombotic regimens and stent types in patients with ST-segment elevation myocardial infarction. A formal intravascular ultrasound (IVUS) substudy enrolled 464 patients with baseline and 13-month follow-up at 36 centers. Of them, 318 patients with 355 lesions were evaluated for this study. Angiographic restenosis occurred in 45 of 355 lesions (12.7%). Bare-metal stent use (45.5% vs 21.2%, p <0.001) and diabetes mellitus (29.5% vs 10.9%, p <0.001) were more prevalent in patients with versus without restenosis. Postprocedure IVUS minimum lumen area (5.6 mm 2, 5.0 to 6.1, vs 6.7 mm 2, 6.5 to 6.9, p <0.001), minimum stent area (5.7 mm 2, 5.1 to 6.3, vs 6.9 mm 2, 6.6 to 7.1, p <0.001), and reference average lumen area (7.7 mm 2, 6.8 to 8.6, vs 9.7 mm 2, 9.3 to 10.1, p <0.001) were smaller in restenotic versus nonrestenotic lesions. By multivariable analysis, minimum stent area was an independent predictor of angiographic restenosis (odds ratio 0.75, 95% confidence interval 0.61 to 0.93, p = 0.009) in addition to diabetes, bare-metal stent use, and longer stent length. Attenuated plaque behind the stent struts had a trend to predict less binary restenosis (p = 0.07). In conclusion, a smaller IVUS minimum stent area was an independent predictor of angiographic restenosis after primary percutaneous intervention in patients with ST-segment elevation myocardial infarction, similar to patients with stable coronary artery disease.