BACKGROUND: Endobronchial ultrasound-guided transbronchial biopsy with a guide sheath (EBUS-GS) is widely used for diagnosing lung cancers; however, the diagnostic yield varies widely. This study aimed to assess the efficiency of EBUS-GS. METHODS: We retrospectively evaluated the results of 110 patients who underwent transbronchial biopsy (TBB) for diagnosis of peripheral lung cancer. Bronchoscopy with and without EBUS-GS was performed in 60 (group A) and 50 patients (group B), respectively; their medical records were examined, and results from the two groups were compared by using the unpaired Student t-test. RESULTS: The diagnostic sensitivity for lung cancer was 83.3% in group A and 68% in group B (P=0.066) while using at least one of the following procedures: TBB, cytological brushing, and bronchial washing. The diagnostic sensitivity for lesions ≥20mm was 86.4% in group A and 76.7% in group B (P=0.263). Moreover, the diagnostic sensitivity for lesions 10-20mm was 60% in group A and 14.2% in group B (P=0.0004); the diagnostic sensitivity with TBB alone was 63.3% in group A and 44% in group B (P=0.043). The diagnostic sensitivity with TBB alone for lesions ≥20mm was 70.2% in group A and 44.8% in group B (P=0.051). Moreover, the diagnostic sensitivity for lesions 10-20mm in size was 45% in group A and 14.2% in group B with TBB alone (P=0.115). CONCLUSION: EBUS-GS with TBB, brushing, and bronchial washing is effective in diagnosing lung cancers sized <20mm.