Uncertainty remains regarding the associations of angiographic optimization and intravascular ultrasound (IVUS) optimization after new-generation drug-eluting stent (DES) implantation.From four randomized trials comparing outcomes between IVUS and angiography-guidance for long or chronic total occlusion (CTO) lesions, 1396 patients who underwent IVUS-guided new-generation DES implantation were enrolled. Of these, 1112 patients (80%) met angiographic optimization criteria (postprocedural diameter stenosis, ≤20%) and were further classified into the matched (same results for angiographic optimization and IVUS optimization) and the mismatched group (opposite results for angiographic optimization and IVUS optimization) according to the meeting of IVUS optimization criteria (minimal stent area, ≥5.5 mm2 or ≥80% of mean reference lumen area). The major adverse clinical events (MACE) were compared.Of 1112 patients with angiographic optimization, 675 patients met the IVUS optimization criteria (61%; matched), but 437 patients (39%; mismatched) failed to meet IVUS optimization criteria (false-positive rate = 76%). On multivariate analyses, age >60 years, reference vessel diameter ≤2.7 mm, left circumflex artery and lesion length ≥33 mm were significant predictors for the mismatched. When comparing the 12-month MACE rates, the mismatched group (6.8%) showed a significantly higher rate than the matched group (1.5%; hazard ratio = 2.62; 95% confidence interval = 1.20-5.72; P = 0.012), mainly driven by a higher target-vessel revascularization rate (6.4 vs 1.4%; P = 0.021).Despite meeting angiographic optimization criteria in long or CTO lesions, more than one-third of the patients with IVUS-guided new-generation DES implantation failed to meet the IVUS optimization criteria and had worse clinical outcomes. Therefore, IVUS optimization should be considered for patients who had predictors of mismatch.