Background: Open lung biopsy is used for diagnosis of diffuse infiltrative lung diseases (DILD), but it is invasive and relatively expensive procedure. Fluoroscopy-guided cutting needle lung biopsy (FCNLB) has merits of avoidance of admission and rapid diagnosis. But diagnostic accuracy and safety were not well known in the diagnosis of DILD. Methods: We included 52 patients (37 men, 15 women) having DILD on HRCT with dyspnea, except the patients who could be confidently diagnosed with clinical and HRCT findings. FCNLB was performed using 16G Ace cut needle (length 1.5 cm, diameter 2 mm) at the area of most active lesion on HRCT. Final diagnoses were made by the consensus. Results: The mean interval between the HRCT and FCNLB was 4.5 days. Most cases were performed one biopsy during 5~10 minutes. Specific diagnosis was obtained in 43 of 52 biopsies (83%). The most common diagnosis was nonspecific interstitial pneumonia (11 cases) and followed by cryptogenic organizing pneumonia (7 cases), diffuse alveolar hemorrhage and usual interstitial pneumonia (5 cases in each), hypersensitivity pneumonitis (3 cases), tuberculosis and drug induced interstitial pneumonitis (2 cases in each), the others are in one respectively. Mild complication was developed in 9 patients (8 pneumothorax, 1 hemoptysis). Most of complications were regressed without treatment except one case with chest tube insertion for pneumothorax. Conclusion: Fluoroscopy-guided 16 G cutting needle lung biopsy was an useful method for the diagnosis of DILD.