OBJECTIVE: To evaluate the effect of rituximab (RTX) in patients with RA-related interstitial lung disease (RA-ILD) and identify factors associated with outcome after treatment. METHODS: An observational study of patients with RA-ILD was conducted from a cohort of RTX-treated RA patients in a single centre for >10 years. Progression was defined by any of the following: a decrease of pre-RTX forced vital capacity (FVC) >10% or diffusion capacity of carbon monoxide (DLCO) >15% predicted, worsening of the ILD score or death from progressive ILD. RESULTS: Of 700 RA patients treated with RTX, 56 had RA-ILD (prevalence = 8%). After RTX, new ILD was diagnosed in 3/700 patients (incidence = 0.4%). Data for lung assessment were available for 44/56 patients. The median relative change pre- and post-RTX for FVC were -2.4% and +1.2% ( P = 0.025) and for DLCO were -4.4% and -1.3% ( P = 0.045). Post-RTX, 23/44 (52%) were stable and 7/44 (16%) had improved. Of the 14 (32%) with ILD that progressed, 9/56 (16%) were deaths due to progressive ILD. Factors associated with ILD progression were radiologic pattern of usual interstitial pneumonia, a previous history of lung progression and pre-RTX DLCO <46% predicted. Of those whose ILD progressed, 11/14 (79%) had severe ILD before RTX [median DLCO 42% predicted (interquartile range 41-49)]. CONCLUSION: In this cohort of patients where RTX was given for arthritis, most patients with ILD pre-RTX remained stable/improved after treatment over a prolonged follow-up period. Patients who deteriorated/died had the most severe ILD pre-RTX, suggesting the drug was not contributory. RTX appears to be an acceptable therapeutic choice for patients with RA-ILD and further studies are warranted.