It has been reported that the internal running vasa vasorum (VV) was associated with plaque vulnerability, and microchannels in optical coherence tomography (OCT) are consistent pathologically with VV. We investigated plaque vulnerability and incidence of slow flow during percutaneous coronary intervention of the internal longitudinal running VV. Subjects were 71 lesions that underwent OCT before percutaneous coronary intervention. Internal running VV was defined as intraplaque neovessels running from the adventitia to plaque. Lesions with internal running VV were found in 47% (33 of 71). Compared with lesions without internal running VV, lesions with internal running VV showed significantly higher incidence of intimal laceration (64% [21 of 33] vs 16% [6 of 38], p <0.001), lipid-rich plaque (79% [26 of 33] vs 26% [10 of 38], p <0.001), plaque rupture (52% [17 of 33] vs 13% [5 of 38], p <0.001), thin-cap fibroatheroma (58% [19 of 33] vs 11% [4 of 38], p <0.001), macrophage accumulation (61% [20 of 33] vs 26% [10 of 38], p = 0.004), intraluminal thrombus (36% [12 of 33] vs 3% [1 of 38], p <0.001), and slow flow after stent implantation (42% [14 of 33] vs 13% [5 of 38], p = 0.007). The multivariable analysis showed that internal running VV was an independent predictor of slow flow after stent implantation (odds ratio 4.23, 95% confidence interval 1.05 to 17.01, p = 0.042). In conclusion, compared with those without, plaques with internal running VV in OCT had high plaque vulnerability with more intimal laceration, lipid-rich plaque, plaque rupture, thin-cap fibroatheroma, macrophage accumulation, and intraluminal thrombus, and they had high incidence of slow flow after stent implantation.