Myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA) is an autoantibody that is frequently found in patients with vasculitides. We encountered some MPO-ANCA positive patients with interstitial pneumonia who lacked vasculitides, but its meaning remains unclear. We measured MPO-ANCA titers in 69 patients with interstitial pneumonia (IP) who did not have collagen vascular diseases and observed their outcome. MPO-ANCA was positive in 5 patients and its prevalence was 7.2%. Patients with MPO-ANCA positive showed higher positivity in rheumatoid factor (RF) than patients with MPO-ANCA negative. The sensitivity and specificity of a combination of anti-nuclear antibody-negative and RF-positive were 80.0% and 87.7%, respectively. Two patients were accompanied by microscopic polyangiitis and the 3-year survival rate was 40% in all patients with MPO-ANCA. Measurement of MPO-ANCA titers in patients with IPs is meaningful for determining therapeutic strategy.