Background Interstitial lung disease in the immunocompetent patient is often a difficult challenge for the clinician, especially when no diagnostic clues are present. A clear diagnosis confirmed by biopsy allows clinicians and patients to discuss fully the implications of the disease. Aim The aim was to evaluate the role of medical thoracoscopic lung biopsy in diagnosis of patients with diffuse parenchymal lung diseases. Patients and methods The study included 15 patients with diffuse parenchymal lung diseases of unknown etiology. They had undergone full history taking, complete clinical examination, ventilatory function tests (spirometry), arterial blood gases analysis, high-resolution computed tomography chest, coagulation profile, platelet count, collagen profile, and thoracoscopic lung biopsy by medical thoracoscopy for histopathologic examination. Follow-up of the patients in the inpatient unit was done by chest radiography and clinical evaluation. Results The pathological diagnosis of cases was six (40%) patients with extrinsic allergic alveolitis, five (33.3%) patients with malignancy, three patients with idiopathic interstitial pneumonias, one (6.7%) patient with tuberculosis, and one (6.7%) patient with sarcoidosis. Regarding complications, one (6.7%) patient had pneumothorax after intercostal tube (ICT) removal, and three (20%) patients had subcutaneous emphysema. The duration of the ICT drainage was 3.1±2.6 days. There was no wound infection, no bleeding, no persistent air leak after more than 24 h (Hs) from ICT insertion, no respiratory failure requiring ICU admission, and no mortality in the study sample. Conclusion Thoracoscopic lung biopsy by medical thoracoscopy is useful in diagnosis of cases with diffuse parenchymal lung diseases of unknown etiology when lung biopsy is needed for accurate diagnosis. The procedure is safe. The procedure carries some complications that are not life threatening and can be minimized by good selection of patients.