AIM: To investigate the efficacy and safety of leflunomide (Lef) in long-term treatm ent of rheumatoid arthritis (RA).　METHODS: Twenty-one patients ［M 2,F 19; age (45±s 9)a］ with RA were s elected. Disease duration was (59±48) mo. All patients enrolled in double-blin d or single-blind trials with Lef 20 mg, po, qd for 6 mo at first. Doses of leflunomide in nine patients were reduced down to 10 mg, qd and all the others c ontinued the treatment with Lef at 20 mg, qd. 　RESULTS: All twenty-one patient s we re followed up for 1.5 a. The results showed that twenty patients had remarkable improvement and one patient had clinical remission. Ni neteen patients had been followed up for more than 2 a and twelve patients had r emarkable improvement while seven patients had clinical remission. Twelve pati ents had been followed up for 3 a and three of them had remarkable improvement while nine patients had clinical remission. Total rate of adverse reactions was 19 %( 4/21). 　CONCLUSION: This study shows that long-term treatment of RA with Lef is effec tive and safe.