Background: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality among women, and early menopause (EM) is associated with an increased risk for ASCVD. Coronary artery calcium (CAC) is a non-invasive measurement of an individual’s subclinical atherosclerotic burden that is used to refine ASCVD risk estimation, and the absence of CAC is a robust predictor of low 10-year ASCVD risk. However, it is unknown whether there is a difference in the long-term association between the absence of CAC and ASCVD risk between women with and without EM. Objectives: To compare the prevalence of CAC and its association with incident ASCVD between women with and without EM. Methods: We performed Kaplan-Meier survival analysis and multivariable Cox proportional hazards modeling using data from 2,456 postmenopausal women in the Multi-Ethnic Study of Atherosclerosis (MESA) with or without EM, defined as occurring at <45 years of age. Results: Participants had a mean age of 64.1 years, 39% were White, and 28% (n=688) experienced EM. There were 291 ASCVD events over a mean follow-up of 12.5 years. Women with EM had a slightly lower prevalence of CAC=0 (55.1%) than women without EM (59.7%) (p=0.04) despite no difference in mean age. Among women with CAC=0, the cumulative incidence of ASCVD was slightly higher at 10-year follow-up for women with vs. without EM (5.4% vs. 3.2%, p=0.06) and significantly higher at 15-years (11.4% vs. 6.4%, p<0.01) (Figure). In multivariable Cox models, compared to women with CAC=0, those with CAC 1-99 and ≥100 had progressively increased ASCVD risk that did not significantly differ by EM status. Conclusions: More than half of postmenopausal women with EM had CAC=0 and an associated low-to-borderline 10-year risk of ASCVD. When CAC>0, the risk of ASCVD was similar for women with and without EM. Additional research is needed to better understand very long-term differences in ASCVD risk between women with and without EM who have CAC=0.