Background and Objectives: Electromagnetic navigation bronchoscopy (ENB) is a promising new technology to increase the diagnostic yield of peripheral lung and mediastinal lesions. Conventional flexible bronchoscopy has a limited yield in peripheral pulmonary lesions, even in experienced hands. Radial endobronchial ultrasound (r-EBUS) with its real-time imaging capability can help to diagnose peripheral pulmonary lesions. In the present study, we aimed to investigate the diagnostic yield and safety of ENB with or without r-EBUS for peripheral lung lesions. Materials and Methods: This study was conducted in a tertiary medical center, and 56 consecutive patients who were thought to be the best candidates for bronchoscopic biopsies at a multidisciplinary meeting were enrolled. ENB was performed under conscious sedation by using an electromagnetic tracking system with multiplanar reconstruction of previously acquired computed tomography (CT) data. Sampling was performed by biopsy forceps, endobronchial brush, and bronchoalveolar lavage. Results: Fifty-six patients (50 men and 6 women; mean age, 60 +/- 9 years) were studied. While an electromagnetic navigation system was used in all patients, r-EBUS was used in 26 of 56 patients. The median diameter of the lesions was 30 mm (interquartile range: 23-44 mm). Mean distance of the lesions from the pleura was 14.9 +/- 14.6 mm. Mean procedure time was 20 +/- 11.5 min. Mean registration error was 5.8 +/- 1.5 mm. Mean navigation error was 1.2 +/- 0.5 mm. The diagnostic yield of the procedure was 71.4% for peripheral lesions (non-small cell lung cancer = 23, small cell lung cancer = 3, benign diseases = 14). Pneumothorax occurred in only 1 patient (1.7%). Conclusion: ENB with or without r-EBUS is a safe, efficient, and easily applied method for sampling of peripheral lung lesions, with high diagnostic yield independent of lesion size and location.