Autopsy studies have suggested that acute myocardial infarction (AMI) represents a pan-coronary process of vulnerable plaque development. We performed multifocal optical coherence tomographic (OCT) examination to compare coronary lesion instability between AMI and stable angina pectoris (SAP). A total of 42 patients with AMI (n = 26) or SAP (n = 16) who had multivessel disease and underwent multivessel coronary intervention were enrolled in the present study. The OCT examination was performed not only in the infarct-related/target lesions, but also in the noninfarct-related/nontarget lesions. OCT-derived thin-cap fibroatheroma (TCFA) was defined as a lesion with a fibrous cap thickness of <65 μm. In the infarct-related/target lesions, plaque rupture (77% vs 7%, p <0.001) and intracoronary thrombus (100% vs 0%, p <0.001) were observed more frequently in AMI than in SAP. The fibrous cap thickness (57 ± 12 vs 180 ± 65 μm, p <0.001) was significantly thinner in AMI and the frequency of OCT-derived TCFA (85% vs 13%, p <0.001) was significantly greater in AMI than in SAP. In the noninfarct-related/nontarget lesions, the frequency of plaque rupture was not different between the 2 groups. Intracoronary thrombus was observed in 8% of AMI, but it was not found in SAP. The fibrous cap thickness (111 ± 65 vs 181 ± 70 μm, p = 0.002) was significantly thinner in AMI and the frequency of OCT-derived TCFA (38% vs 6%, p = 0.030) was significantly greater in AMI than in SAP. Multiple OCT-derived TCFAs in both the infarct-related/target and the noninfarct-related/nontarget lesions were observed in 38% of patients with AMI but not in patients with SAP (p = 0.007). In conclusion, the present OCT examination demonstrated multiple lesion instability in the presence of AMI.