The purpose of this study way to assess the value of contrast enhanced gray-scale ultrasound (CEUS) in detection of vascularity in joints of patients with rheumatoid arthritis (RA) in a multicenter study of the International Arthritis Contrast Ultrasound (IACUS) study group. We assessed 113 joints in 113 patients (44 men, 69 women; mean age 51+/-14 years) with clinical diagnosis of RA. Gray-scale ultrasound (US), power Doppler US (PDUS) and CEUS, using a low mechanical index US technique, was performed. CEUS was done by bolus administration of the contrast agent SonoVue (Bracco, Milan, Italy) with a dosage of 4.8-ml SonoVue flushed with 10 ml saline. Detection of joint vascularity was performed for differentiation of active synovitis from inactive intra-articular thickening (synovitis/effusion). With the use of US and PDUS, active synovitis could be differentiated from inactive intra-articular thickening in 68/113 joints (60.1%), whereas CEUS enabled differentiation in 110/113 (97.3%) joints (p<0.0001). Thickness measurement of active synovitis was significantly improved after contrast administration (p=0.008). In conclusion, CEUS improves the differentiation of active synovitis from inactive intra-articular thickening. Since CEUS has shown an ability to improve assessment of vascularized synovial proliferation in RA affected joints, this technique may have further potential in monitoring therapy.