Abstract Background Menopausal vasomotor symptoms (VMS) have been associated with subclinical and manifest atherosclerotic cardiovascular disease (ASCVD) but the scientific basis is limited and VMS have not been studied in relation to image-detected coronary atherosclerosis. PURPOSE To assess, in peri- and postmenopausal women, associations between VMS and subclinical ASCVD detected through computed tomography angiography (CCTA), coronary artery calcium score (CACS) or carotid ultrasound, and if potentially determined associations are modified by menopausal hormone therapy (MHT) or regular physical activity (PA). Methods This cross-sectional population-based study was conducted on a subset of participants from the Swedish CArdioPulmonary BioImage Study (SCAPIS), including women 50-65 years of age. The women underwent comprehensive cardiovascular assessments and completed an extensive questionnaire, which included questions about current and previous menopause-related symptoms. VMS was assessed on a 4-point scale and analyzed in relation to subclinical ASCVD, detected via CCTA, CACS and carotid ultrasound using multivariate logistic regression analyses. Results Of 2995 women included, 14.2% reported severe VMS (n= 425), 18.1% moderate VMS (n=543), and 67.7% no or mild VMS (n=2027). Women with severe, but not those with moderate, VMS had higher prevalence of CCTA detected atherosclerosis (34.1% vs 27.8%, p<0.05), but not CACS >100 (5.8% vs 6.6% p >0.05) or any carotid plaque (47.6% vs 46.6%, p>0.05) than women with no or mild VMS. Using the same reference category, severe but not moderate VMS was significantly associated with CCTA-detected atherosclerosis, odds ratio (OR) before and after multivariable adjustment 1.36, 95% confidence interval (CI) 1.08 – 1.72 and 1.33, 95% CI 1.02 – 1.72, respectively. This association became stronger when requiring an over 5-year duration of severe VMS, multivariable adjusted OR 1.53, 95% CI 1.09 – 2.14. Additional adjustment for MHT strengthened the association (OR 1.64, 95% CI 1.16 – 2.32). No significant association with CACS >100 or with the presence of any carotid plaque was observed. Additional adjustment for PA did not change any associations. Conclusions Severe but not moderate VMS were significantly associated with CCTA detected atherosclerosis, independent of a broad range of cardiovascular risk factors. Further research is required to determine the eventual causality of this relationship.Figure 1.Forest plots