At present, no studies have evaluated the role of bronchoscopic transbronchial lung biopsy (TBLB) in the diagnosis of diffuse drug-induced lung disease (DILD), and there is no consensus for a definite diagnostic workup approach for this rare clinical entity. The aim of the present study was to evaluate the clinical usefulness of TBLB in diffuse DILD. This study was a retrospective analysis of patients with diffuse DILD, who underwent bronchoscopy. The role of TBLB was assessed to determine whether the histological results are useful for the final diagnosis. Over a 5-yr period, 44 patients underwent bronchoscopy, and all had a bronchoalveolar lavage (BAL). Thirty-three of the 44 patients underwent TBLB (75%), and the results of TBLB were diagnostically helpful in 25 (75.7%) of the procedures. No histopathologic abnormality was identified in 6 (18%) of the 33 patients. In 2 patients (6%) the obtained samples were not adequate, since no lung parenchyma was obtained. No severe complications related to bronchoscopic procedures occurred. In conclusion, TBLB is a safe procedure, and is diagnostically helpful in the majority of cases of patients with diffuse DILD. Histological data obtained by TBLB further corroborate clinical, laboratory, radiologic and BAL results for a definitive diagnosis of diffuse DILD.