ABSTRACT Background: This study assesses whether pineal gland calcification (PGC) - a surrogate for reduced endogenous melatonin production - is associated with significant stenosis of large intracranial arteries - a biomarker of intracranial atherosclerotic disease (ICAD). Methods: Individuals aged ≥60 years enrolled in the Three Villages Study received head CT to assess PGC and MRA to estimate stenosis of large intracranial arteries. Multivariate logistic regression models were fitted to assess the association between PGC and ICAD, after adjusting for relevant confounders. Inverse probability of exposure weighting was used to estimate the effect of PGC on ICAD. Results: A total of 581 individuals were enrolled. PGC and ICAD were associated in a fully-adjusted logistic regression model (p=0.032). Inverse probability of exposure weighting showed an estimate for the proportion of ICAD among those without PGC of 3.7% and the adjusted-effect coefficient was 5.7% higher among those with PGC (p=0.031). Conclusions: PGC is associated with ICAD. Study results provide grounds for evaluating the role of melatonin deficiency in ICAD progression.