ObjectivesThe relationship between rheumatoid arthritis (RA) and coronary atherosclerosis is widely concerned, but observational studies have not clarified causality. We performed two-sample Mendelian randomization (MR) study to assess the causal association between RA and coronary atherosclerosis.Methodswe mainly conducted MR analysis using the inverse variance weighted (IVW) approach. Weighted median, MR-Egger regression and maximum likelihood were conducted as sensitivity analyses for supplementary analysis. Multivariate MR also were performed to validate the results of two-sample MR. Furthermore, we performed the MR-Egger intercept, MR-PRESSO, Cochran's Q test, and “Leave-one-out” to assess the levels of pleiotropy and heterogeneity.ResultsIVW result showed a positive link between genetic predisposition to RA and increased relative risk of coronary atherosclerosis (OR: 1.0021, 95%CI 1.0011-1.0031, P < 0.05). The result was confirmed by the weighted median method (OR: 1.0028, 95%CI 1.0014-1.0042, P < 0.05), MR-Egger regression (OR: 1.0031, 95%CI 1.0012-1.0049, P < 0.05) and maximum likelihood (OR: 1.0021, 95%CI 1.0011-1.0030, P < 0.05). Multivariate MR also reached a consistent conclusion. In addition, MR-Egger intercept (P = 0.20) and MR-PRESSO (P = 0.06) did not provide evidence of horizontal pleiotropy. Meanwhile, the results of Cochran's Q test (P = 0.05) and “Leave-one-out” failed to detect significant heterogeneity.ConclusionThe result of the two-sample MR analysis found genetic evidence to support the positive causal association between RA and coronary atherosclerosis, suggesting that active intervention for RA may reduce the incidence of coronary atherosclerosis.