Interstitial lung disease (ILD) is a frequently encountered and sometimes life-threatening complication among patients with rheumatoid arthritis (RA). In this study, we aim to clarify the incidence of and risk factors for ILD using a large observational cohort of RA patients. We analyzed the database from a large observational cohort of Japanese RA patients, the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) cohort. We defined as interstitial pneumonia (IP) computed tomography (CT) pattern of nonspecific interstitial pneumonia or diffuse alveolar damage. Newly developed IP was identified from patient reports over 2.5 years (April 2004 to October 2006) and was confirmed by extensive medical record, chest X-ray radiograph, and CT. The raw and age/gender-adjusted incidence of IP were reported. IP risk factors were analyzed using a nested case-control design was employed using conditional logistic regression analysis with a stepwise method. Thirty-seven patients among 5,699 RA patients were diagnosed with newly developed IP, including 18 cases with methotrexate-induced pneumonitis (MTX-IP) and 15 cases with IP associated with RA (RA-IP). The age-adjusted incidence of MTX-IP among total patients, males, and females was 3.775, 6.667, and 1.013 per 1,000 cases, respectively, and of RA-IP among total patients, males, and females was 1.056, 1.452, and 0.677 per 1,000 cases, respectively. Conditional logistic regression analysis after stepwise variable selection identified male gender, increased Japanese version of the Health Assessment Questionnaire (J-HAQ) score, decreased pain visual analog scale (VAS), and elevated erythrocyte sedimentation rate as significant risk factors for MTX-IP, while the only risk factor for RA-IP was male gender. The incidence of and risk factors for IP in RA patients were determined in a large observational cohort of RA patients in Japan.