Background The frequent occurrence of calcification in intracranial artery stenosis increases the risk of ischemic stroke. In previous cases, we have observed a possible relationship between calcification and intracranial in-stent restenosis (ISR) using optical coherence tomography (OCT). Therefore, our study aimed to demonstrate the relationship between intracranial calcification and ISR with a larger sample size.Methods For our study patients who underwent OCT for intracranial artery stenosis before stenting were included from May 2020 to October 2022. Follow-up assessments were performed using transcranial color-coded duplex (TCCD) sonography ultrasonography to detect cases of ISR.Results We recruited 54 patients, 15 of them were excluded as they did not meet the study criteria. Our study included 39 patients, of whom 21 had calcification, and 18 did not. The results of our study revealed a significant association between calcification and intracranial ISR (9 (42.86) vs 2 (11.11), p=0.0375). Notably, patients with macrocalcification were more likely to undergo ISR than patients with spotty calcification (77.78% vs 22.22%, p=0.03).Conclusion OCT imaging demonstrates that calcification is an essential risk factor for intracranial ISR. These findings have important implications for individualized treatment. They provide valuable insights for optimizing stent design and exploring potential mechanisms of intracranial ISR.