Background: In order to study the mechanisms and morphological aspects of the in-stent restenosis (ISR) have been evaluated restenosis lesions referred to drug eluting stent (DES) of the first generation using optical coherence tomography technique (OCT). Material and methods: The study underwent 39 patients with ISR induced recurrent angina or acute coronary syndrome including 66 stents from which were: 44 stents (28 patients) of the first generation of DES (19 – Cypher TM and 23 – Taxus®), and 22 stents (11 patients) of the second DES generation (9 Xience TM 2 Promus TM), 10 ZES (Resolute TM), and one stent Nobori TM. Has been made quantitative and morphological analysis of tissue pattern of ISR using the following OCT criteria: 1) morphologically homogenous neointima; 2)morphologically heterogeneous neointima; and 3) neoatherosclerosis. Results: It has been established that in the first generation of DES morphological homogenous pattern was present in both ISR developed after 1 year and later. However, the optical aspect with heterogeneous presentation had a prevalence decline in dynamics. The heterogeneous model had a higher prevalence in actual generation of DES in both incipient (< 1 year) and late presentation. Conclusions: The phenomenon of neoatherosclerosis has presented a significantly less frequency in the late restenosis of actual generation of DES. Our results suggest that restenosis phenomenon in actual generation of DES has a different morphological and evolution pattern in time in comparison with ISR of the first generation of DES.