Background: The value of joint ultrasonography (US) in the prediction of clinical arthritis in individuals at risk of developing rheumatoid arthritis (RA) is still a point of debate, due to varying scanning protocols and different populations. We investigated whether US abnormalities assessed with a standard joint protocol can predict development of arthritis in seropositive patients with arthralgia. Methods: Anti-citrullinated protein antibodies and/or rheumatoid factor positive patients with arthralgia, but without clinical arthritis were included. US was performed at baseline in 16 joints: bilateral metacarpophalangeal 2-3, proximal interphalangeal 2-3, wrist and metatarsophalangeal (MTP) joints 2-3 and 5. Images were scored semi-quantitatively for synovial thickening and for positive signs on power Doppler (PD). Association between US abnormalities and arthritis development at the joint and at the patient level was evaluated. Also, we investigated the added value of US over clinical parameters. Results: Out of 163 patients who underwent US examination, 51 (31%) developed clinical arthritis after a median follow-up time of 12 (interquartile range 5-24) months, of which 44 (86%) satisfied the 2010 American College of Rheumatology/European League Against Rheumatism classification criteria for RA. US revealed synovial thickening and PD in at least one joint in 49 patients (30%) and 7 patients (4%), respectively. Synovial thickening was associated with both development and timing of clinical arthritis in any joint (patient level) when MTP joints were excluded from the US assessment (odds ratio 6.6, confidence interval (CI) 1.9-22), and hazard ratio 3.4, CI 1.6-6.8, respectively, with a mean time to arthritis of 23 versus 45 months when synovial thickening was present versus not present). There was no association between US and arthritis development at the joint level. Predictive capacity was highest in the groups with an intermediate and high risk of developing arthritis based on a prediction rule with clinical parameters. Conclusions: Synovial thickening on US predicted clinical arthritis development at the patient level in seropositive patients with arthralgia when MTPs were excluded from the US assessment. Positive PD signs were infrequently seen in these at-risk individuals and was not predictive. In patients at intermediate risk of RA, US may help to identify those at higher risk of developing arthritis.