Irregular protrusion on optical coherence tomography (OCT) is associated with clinical events and target lesion revascularization. We investigated clinical and procedure characteristics, plaque characteristics, slow flow after stent implantation, and clinical outcomes with irregular protrusion using OCT. Eighty-four lesions in 76 patients undergoing OCT before percutaneous coronary intervention were evaluated. Irregular protrusion was defined as protrusion of material with an irregular surface into the lumen between stent struts with a maximum height of ≥100 μm. Lesions with irregular protrusion were found in 56% (47/84). Compared with lesions without irregular protrusion, those with irregular protrusion had significantly higher low-density lipoprotein cholesterol (LDL-C) levels (108 ± 31 mg/dl vs. 95 ± 25 mg/dl, P = 0.044); a tendency toward decreased use of statins [44% (19/43) vs. 67% (22/33), P = 0.065]; significantly larger reference vessel diameter (3.12 ± 0.53 mm vs. 2.74 ± 0.63 mm, P = 0.004); more frequent slow flow after stent implantation [38% (18/47) vs. 11% (4/37), P = 0.006]; higher incidence of thin-cap fibroatheromas [TCFAs; 49% (23/47) vs. 5% (2/37), P < 0.001]; plaque rupture [40% (19/47) vs. 16% (6/37), P = 0.018]; and a tendency higher incidence of 1-year adverse clinical outcomes (death, acute myocardial infarction, acute coronary syndrome, or target lesion revascularization) [12% (5/43) vs. 0% (0/33), P = 0.075]. In conclusion, irregular protrusion on OCT was associated with high plaque vulnerability, higher LDL-C, less frequent use of statin, larger vessel diameter, slow flow after stent implantation, and 1-year adverse clinical outcomes.