PURPOSE:: To characterize the cardiorespiratory response to exercise before and after aerobic exercise training in patients with interstitial lung disease. METHODS:: We performed a clinical study, examining 13 patients (New York Heart Association/World Health Organization Functional class II or III) before and after 10 weeks of supervised treadmill exercise walking, at 70% to 80% of heart rate reserve, 30 to 45 minutes per session, 3 times a week. Outcome variables included measures of cardiorespiratory function during a treadmill cardiopulmonary exercise test, with additional near infrared spectroscopy measurements of peripheral oxygen extraction and bioimpedance cardiography measurements of cardiac output. Six-minute walk test distance was also measured. RESULTS:: All subjects participated in at least 24 of their 30 scheduled exercise sessions with no significant adverse events. After training, the mean 6-minute walk test distance increased by 52 ± 48 m (P = .001), peak treadmill cardiopulmonary exercise test time increased by 163 ± 130 s (P = .001), and time to achieve gas exchange threshold increased by 145 ± 37 s (P < .001). Despite a negligible increase in peak (Equation is included in full-text article.)o2 with no changes to cardiac output, the overall work rate/(Equation is included in full-text article.)o2 relationship was enhanced after training. Muscle O2 extraction increased by 16% (P = .049) after training. CONCLUSIONS:: Clinically significant improvements in cardiorespiratory function were observed after aerobic exercise training in this group of subjects with interstitial lung disease. These improvements appear to have been mediated by increases in the peripheral extraction of O2 rather than changes in O2 delivery.