Ethnopharmacological relevance: The exploration of risk factors on the gastrointestinal adverse drug reactions (Cl ADRs) and hepatic ADRs in the treatment of rheumatoid arthritis (RA) with traditional Chinese medicien (CM) and convertional Western Medicien (WM) therapy will benifit the clincial drug administration. Methods: A multi-center, randomized-clinical trial was conducted on RA patients in China. After 12 and 24 weeks of treatment, the efficacy and safety of WM therapy and CM therapy were evaluated. The Chi-square and logistic regression were conducted to analyze the correlations between the biological parameters. CM symptoms and the ADRs. Results: 505 patients were recruited from 9 centers and randomly assigned into WM therapy group (n=251) or CM group (n=254). 397 of them completed the 24 week treatment (194 in WM and 203 in CM group). Total ADRs incidence and withdrawal rates were similar in two groups. For the patients treated with WM, logistic regression analysis showed that CRP level was negatively related to GI ADRs (p<0.05), dizziness was positively related to GI ADRs (p<0.05); and IgG level and chills were positively related to hepatic ADRs (p<0.01, p<0.05). In the patients treated with CM, no laboratory measurements were found related with GI ADRs and hepatic ADRs, lassitude and nocturia were risk factors for GI ADRs, cold extremities for hepatic ADRs, respectively (p<0.05). Conclusion: CRP in normal scale and dizziness were the risk factors for GI ADRs, higher IgG level and chills were the risk factors for hepatic ADRs in the RA patients treated with conventional WM therapy. Lassitude and nocturia were the risk factors for GI ADRs, and cold extremities were the risk factors for hepatic ADRs in the RA patients treated with CM therapy. (C) 2011 Elsevier Ireland Ltd. All rights reserved.