Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive form of interstitial lung disease (ILD). High-resolution CT (HRCT) is currently used to identify macroscopic IPF features. However, for 50% of patients, ultimate diagnosis relies on microscopic features from invasive, high-risk surgical biopsies (SLBX). We conducted a pilot study to assess endobronchial OCT (EB-OCT) for in vivo diagnosis of IPF, enrolling ILD patients with nondiagnostic HRCT undergoing SLBX. EB-OCT visualized salient IPF features, including microscopic features not visible on HRCT, and accurately diagnosed IPF and non-IPF ILD as compared with SLBX. EB-OCT has the potential for in vivo microscopic diagnosis of IPF.