Background: The increased mortality observed in patients with rheumatoid arthritis is partly due to an increased occurrence of serious infections. A retrospective study from the Mayo Clinic found that infection risk is increased in rheumatoid arthritis. In particular, serious infection was associated with severe disease and use of corticosteroids. Robust estimates are required from prospective studies of incident cases. Objective: To examine the risk of infection leading to hospitalisation and potential factors associated with this risk in an unselected population of patients with inflammatory polyarthritis. Design: A prospective cohort study comparing infection incidence in new-onset patients with inflammatory polyarthritis with local population experience. Patients and methods: 2108 patients with inflammatory polyarthritis from a community-based register were studied and followed up annually (median 9.2 years). The rate of hospitalisations for serious infection was compared with the rate of hospitalisations in the regional population. The contribution of potential predictors was assessed by undertaking a within-cohort analysis. Results: Overall, the incidence of infection was more than two and a half times that of the general population (varying by site). History of smoking, corticosteroid use and rheumatoid factor were found to be significantly independent predictors of infection-related hospitalisation. Patients with inflammatory polyarthritis with all three factors were more than seven times as likely to be hospitalised compared with the rest of the cohort. Discussion: These findings provide background data on the risk of infection associated with rheumatoid arthritis, and are of particular interest given the current awareness of the risk of infection associated with antitumour necrosis factor alpha treatments.