Background—Impact of plaque composition on late acquired stent malapposition (LSM) after drug-eluting stent (DES) implantation has not been evaluated. Methods and Results—We evaluated the relation between plaque components at poststenting peristent area (between external elastic membrane and stent areas) and LSM after DES implantation in 266 patients (314 native lesions; paclitaxel-eluting stent in 205 lesions, sirolimus-eluting stent in 66 lesions, zotarolimus-eluting stent in 32 lesions and everolimus-eluting stent in 11 lesions) in whom virtual-histology intravascular ultrasound was performed at index and 12-month follow-up. LSM occurred in 24 patients with 30 lesions (9.6%) and there were no significant differences in the incidences of LSM among 4 DES groups [21/205 (10.2%) in paclitaxel-eluting stent, 6/66 (9.1%) in sirolimus-eluting stent, 2/32 (6.3%) in zotarolimus-eluting stent and 1/11 (9.1%) in everolimus-eluting stent, P=0.5)]. Patients with LSM were presented with more acute myocardial infarction (50% versus 28%, P=0.026) and were more diabetics (50% versus 30%, P=0.030) and used multiple stents (40% versus 16%, P=0.001) and overlapping stents (40% versus 14%, P<0.001) more frequently compared with those without LSM. Lesions with LSM had more poststenting peristent %necrotic core (NC) volume compared with those without LSM (25.8짹11.1% versus 21.0짹5.7%, P<0.001). Independent predictors of LSM were poststenting peristent %NC volume [odds ratio (OR); 1.216, 95% CI; 1.053-1.405, P=0.008], acute myocardial infarction (OR; 2.897, 95% CI; 1.675-4.118, P=0.029), and diabetes mellitus (OR; 2.413, 95% CI; 1.543-3.996, P=0.038). Conclusions—Poststenting peristent NC components, myocardial infarction, and diabetes mellitus were associated with the development of LSM after DES implantation.