The purpose of this study was to investigate the feasibility of diffusion-weighted imaging (DWI) in detecting synovitis of wrist and hand in patients with rheumatoid arthritis (RA) and evaluate its sensitivity, specificity and accuracy as compared to T2-weighted imaging (T2WI) with short tau inversion recovery (STIR) with the reference standard contrast-enhanced magnetic resonance imaging (CE-MRI). Twenty-five patients with RA underwent MR examinations including DWI, T2WI with STIR and CE-MRI. MR images were reviewed for the presence and location of synovitis of wrist and hand. The sensitivity, specificity and accuracy of DWI and T2WI with STIR were calculated respectively and then compared. All patients included in this study completed MR examinations and yielded diagnostic image quality of DWI. For individual joint, there was good to excellent inter-observer agreement (k=0.62–0.83) using DWI images, T2WI with STIR images and CE-MR images, respectively. There was a significance between DWI and T2WI with STIR in analyzing proximal interphalangeal joints II–V, respectively (P<0.05). The k-values for the detection of synovitis indicated excellent overall inter-observer agreements using DWI images (k=0.86), T2WI with STIR images (k=0.85) and CE-MR images (k=0.91), respectively. Overall, DWI demonstrated a sensitivity, specificity and accuracy of 75.6%, 89.3% and 84.6%, respectively, for detection of synovitis, while 43.0%, 95.7% and 77.6% for T2WI with STIR, respectively. DWI showed positive lesions much better and more than T2WI with STIR. Our results indicate that DWI presents a novel non-invasive approach to contrast-free imaging of synovitis. It may play a role as an addition to standard protocols.