BACKGROUND: Pulmonary rehabilitation improves functional capacity and symptoms in the interstitial lung diseases (ILDs), however there is marked variation in outcomes between individuals. The aim of this study was to establish the impact of the aetiology and severity of ILD on response to pulmonary rehabilitation. METHODS: Forty-four subjects with ILD, including 25 with idiopathic pulmonary fibrosis (IPF), underwent eight weeks of pulmonary rehabilitation. Relationships between disease aetiology, markers of disease severity and response to pulmonary rehabilitation were assessed after eight weeks and six months, regardless of program completion. RESULTS: In IPF, greater improvements in 6-minute walk distance (6MWD) immediately following pulmonary rehabilitation were associated with larger forced vital capacity (r = 0.49, p = 0.01), less exercise-induced oxyhaemoglobin desaturation (r(S) = 0.43, p = 0.04) and lower right ventricular systolic pressure (r = -0.47, p = 0.1). In participants with other ILDs there was no relationship between change in 6MWD and baseline variables. Less exercise-induced oxyhaemoglobin desaturation at baseline independently predicted a larger improvement in 6MWD at six month follow-up. Fewer participants with IPF had clinically important reductions in dyspnoea at six months compared to those with other ILDs (25% vs 56%, p = 0.04). More severe dyspnoea at baseline and diagnosis other than IPF predicted greater improvement in dyspnoea at six months. CONCLUSIONS: Patients with IPF attain greater and more sustained benefits from pulmonary rehabilitation when disease is mild, whereas those with other ILDs achieve benefits regardless of disease severity. Early referral to pulmonary rehabilitation should be considered in IPF.