The relationship between frailty and plaque characteristics is unclear and was investigated by optical coherence tomography (OCT) in this study. One hundred and four patients undergoing OCT before percutaneous coronary intervention were evaluated. Frailty was defined as a clinical frailty scale score of ≧6. Frailty was found in 16% of the patients (17/104). Compared with the nonfrail patients, frail patients showed significantly lower body mass index (BMI; 20.8 ± 4.0 kg/m2 vs. 25.0 ± 3.9 kg/m2, P < 0.001), less dyslipidemia [47% (8/17) vs. 75% (65/87), P = 0.023], lower triglycerides levels (95 ± 42 mg/dL vs. 147 ± 81 mg/dL, P < 0.001), less use of statin [29% (5/17) vs. 60% (52/87), P = 0.021], more lipid-rich plaque [82% (14/17) vs. 46% (40/87), P = 0.006] on OCT, more thin-cap fibroatheromas [TCFAs; 71% (12/17) vs. 26% (23/87), P < 0.001], more plaque rupture [53% (9/17) vs. 25% (22/87), P = 0.023], and significantly higher adverse clinical outcomes (death, acute myocardial infarction, acute heart failure, acute coronary syndrome, or target lesion revascularization) [24% (4/17) vs. 6% (5/87), P = 0.007]. The multivariable analysis showed that frailty was one of the independent predictors of TCFAs (odds ratio 8.95, 95% CI 2.40–33.32, P = 0.001). In conclusion, frailty was associated with high plaque vulnerability due to more lipid-rich plaque, TCFAs and plaque rupture on OCT regardless of low BMI, less dyslipidemia and low triglycerides levels, and frail patients had higher adverse clinical outcomes.