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Abstract Background Patients with rheumatoid arthritis (RA) have an increased risk of coronary artery disease (CAD) above the baseline. Baicalin possesses beneficial effects against both RA and CAD, but little is know on its clincial efficacy among patients manifesting both CAD and RA. Methods Three hundred seventy four patients with CAD and RA were randomized to receive either 500 mg baicalin or placebo orally everyday for 12 weeks. Lipid profile, cardiotrophin-1 (CT-1), high sensitivity C-reactive protein (hs-CRP), European League Against Rheumatism (EULAR) response were analyzed at the end of study period. Results After 12 week treatment, levels of triglycerides, total cholesterol, LDL-cholesterol and apolipoproteins, as well as CT-1 and hs-CRP, were all significantly improved in the baicalin group compared to the placebo group (1.12 ± 0.36 vs 1.87 ± 0.46 mmol/L, 2.87 ± 1.23 vs 3.22 ± 1.07 mmol/L, 1.38 ± 0.41 vs 1.16 ± 0.32 mmol/L, 1.31 ± 0.41 vs 1.23 ± 0.29 g/L, 42.9 ± 13.7 vs 128.4 ± 24.3 ng/mL, 1.64 ± 0.38 vs 3.9 ± 1.4 mg/dL, respectively). Significantly higher proportion of patients in the baicalin group (71%) reported good/moderate EULAR response than the placebo group (53%). Conclusion Baicalin reduces blood lipids and inflammation in patients with both CAD and RA, supporting its further clinical application.