BackgroundZhengqing Fengtongning (ZF) is a modern traditional Chinese medicine preparation used to treat rheumatoid arthritis (RA). In this study, we aimed to prove the effectiveness of ZF in combination with routine RA treatment in the real world. MethodsThis was a retrospective study including 3877 RA patients in multi-centers from August 2015 to April 2023. The experimental group received ZF and the control group received other RA regimens. Propensity score matching was used to eliminate bias. The effectiveness of ZF in combination with routine RA treatment was evaluated through DAS28, ESR, CRP and RF. ResultsThe effectiveness of combining ZF with methotrexate (MTX), iguratimod (IGU), leflunomide (LEF), MTX + LEF, and MTX + nonsteroidal anti-inflammatory drugs in treating RA was significantly better than that of not combining ZF (p < 0.05). The effectiveness of combining ZF was significantly better than that of combining total glucosides of paeony, Kunxian capsule, or Biqi capsule (p < 0.05). No significant difference existed in effectiveness among MTX, IGU, and ZF combined with JAK inhibitor or TNF-ɑ inhibitor (p > 0.05). ConclusionsThis study provides evidence that the effectiveness of MTX, IGU, LEF, MTX + LEF, and MTX + NSAIDs combined with ZF in treating RA was better than those without ZF.