The phenomenon to heal neointimal rupture or thrombus after coronary stenting occurs as well as in native coronary artery. We investigated clinical characteristics and neointimal vulnerability of healed neointima by optical coherence tomography (OCT). We treated 67 lesions by percutaneous coronary intervention for in-stent restenosis (ISR) and conducted OCT examinations. Healed neointima was defined as neointima having one or more layers with different optical densities and a clear demarcation from underlying components. ISR with healed neointima was found in 49% (33/67) of the lesions. Compared to ISR without healed neointima, ISR with healed neointima showed significantly longer stent age (102 ± 72 vs. 31 ± 39 months, P < 0.001), lower frequency of dual antiplatelet therapy [42% (14/33) vs. 74% (25/34), P = 0.017], lower use of angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker (ACE-I or ARB) [61% (20/33) vs. 91% (31/34), P = 0.028], lower usage of second-generation drug-eluting stents (DESs) [36% (12/33) vs. 63% (22/34), P = 0.029], higher usage of thick-strut stents [42% (14/33) vs. 15% (5/34), P = 0.012], larger neointimal area (6.8 ± 2.6 vs. 5.2 ± 1.8 mm², P = 0.005), higher incidence of thin-cap fibroatheroma [58% (19/33) vs. 21% (7/34), P = 0.002], neointimal rupture [45% (15/33) vs. 9% (3/34), P = 0.001], and lower incidence of stent underexpansion [15% (5/33) vs. 44% (15/34), P = 0.010]. In conclusions, ISR with healed neointima was associated with neointimal vulnerability, stent age, stent type, stent strut thickness, stent expansion, antiplatelet therapy, and use of ACE-I or ARB.