OBJECTIVE: Rheumatoid cachexia (muscle wasting) in rheumatoid arthritis (RA) patients contributes to substantial reductions in strength and impaired physical function. The objective of this randomized controlled trial was to investigate the effectiveness of oral creatine (Cr) supplementation in increasing lean mass and improving strength and physical function in RA patients. METHODS: In a double-blind design, 40 RA patients were randomized to either 12 weeks' supplementation of Cr or placebo. Body composition (dual x-ray absorptiometry and bioelectrical impedance spectroscopy [BIS]), strength, and objectively assessed physical function were measured at baseline, day 6, week 12, and week 24. Data analysis was performed by analysis of covariance. RESULTS: Cr supplementation increased appendicular lean mass (ALM; a surrogate measure of muscle mass) by mean ± SE 0.52 ± 0.13 kg (P = 0.004 versus placebo), and total LM by 0.60 ± 0.37 kg (P = 0.158). The change in LM concurred with the gain in intracellular water (0.64 ± 0.22 liters; P = 0.035) measured by BIS. Despite increasing ALM, Cr supplementation, relative to placebo, failed to improve isometric knee extensor strength (P = 0.408), handgrip strength (P = 0.833), or objectively assessed physical function (P = 0.335-0.764). CONCLUSION: In patients with RA, Cr supplementation increased muscle mass, but not strength or objective physical function. No treatment-related adverse effects were reported, suggesting that Cr supplementation may offer a safe and acceptable adjunct treatment for attenuating muscle loss; this treatment may be beneficial for patients experiencing severe rheumatoid cachexia.