Introduction: Rheumatoid arthritis (RA) is an autoimmune disease characterized by progressive bone erosion on diarthrodial joints. RA patients usually experienced three stages before final diagnosis: the health period, the pre-clinical period (immune response exists without clinical symptoms), and the pre-RA period (immune response exists with mild inflammatory manifestation). Presently, there is seldom guidance referring to early intervention which is a benefit for stable disease conditions and low morbidity. Prophylactic treatment is a major feature of traditional Chinese medicine (TCM). In this present study, a multi-center, double-blind, placebo-controlled clinical trial is carried out to evaluate both efficacy and safety in preventing RA progression on Yunpi Qufeng Chushi formula (YQCF). Method: The multi-center, double-blind, placebo-controlled clinical trial is conducted in 13 hospitals nationwide. A total of 390 patients ages between 18 and 70 will be recruited in the trial. They will be randomly assigned to the intervention group (YQCF) and placebo group. The follow-up visit will be taken every 3 months from baseline to 1 year. Diagnosis, disease activity scores, clinical disease activity index (CDAI), simplified disease activity index (SDAI), TCM syndrome scores, and safety assessments will be recorded at every visit. Joint color doppler ultrasound, health assessment questionnaire-disability index (HAQ-DI), and functional assessment of chronic illness therapy-fatigue (FACIT-F) will be recorded at baseline and the last visit. Discussion: This work will provide evidence of YQCF in preventing RA progression. However, whether early intervention would benefit the controlling RA disease still needs a long-term follow-up. Ethics and dissemination: Protocol version 2 (201910-1). This research was approved by the medical ethics committee of Zhejiang Chinese Medical University (2019-045). Results will be published in a peer-reviewed academic journal.