We evaluated early vascular responses after new-generation drug-eluting stent (DES) implantation. From 2 randomized trials, we identified 471 patients (138 patients with acute myocardial infarction [AMI] vs 333 patients with stable angina or unstable angina [SA/UA]) treated by DESs who underwent serial optical coherence tomography (OCT) from postprocedure to 3 months. At 3-month follow-up OCT, malapposed strut percentage was higher in AMI than in SA/UA (5.3% vs 0.7%, P < .001); it was markedly increased from postprocedure in AMI (2.0%-5.3%, P < .001), whereas it decreased in SA/UA (1.7%-0.7%, P < .001). Patients with AMI showed a higher risk of persistent (59% vs 37%; P < .001) or late-acquired malapposition (15% vs 8%; P = .04). Uncovered strut percentage at 3 months was also higher in AMI than in SA/UA (13.1% vs 6.7%, P < .001). The AMI presentation was the significant risk factor for both significant stent malapposition (SM, ≥200 μm; odds ratio [OR] = 3.45, CI = 1.85-7.14, P < .001) and uncovered stent (% uncovered struts >6.0%; OR = 2.44, CI = 1.35-4.76, P = .004), together with malapposed distance and postprocedural thrombi. Further, AMI presentation was the predictor for the occurrence of early period late-acquired and persistent malapposition. Serial OCT comparison analyses showed that patients with AMI compared with patients with SA/UA showed more delayed strut coverage, more severe degree SM or uncovered stents, and higher incidences of early period persistent or late-acquired SM.