The role of video-thoracoscopy (VT) as an invasive diagnostic procedure for mediastinal lesions not reachable by cervical mediastinoscopy (CM) has still to be defined, particularly with regard to parasternal mediastinotomy (PMT). Diagnostic efficiency and morbidity of the three methods were assessed and compared in a consecutive series over a 18 months-period after determination of a new diagnostic strategy. Among 77 interventions in 73 patients the following distribution of the methods referred was achieved: 42 CM (paratracheal and anterior subcarinal biopsies), 17 PMT (biopsies of anterior mediastinal lesions) and 18 VT (3 paratracheal, 3 posterior subcarinal, 3 anterior, 5 aortico-pulmonary window, 4 posterior biopsies or resections). All procedures were performed in general anesthesia for VT the double-lumen technique was used. Drains could be removed not later than the second postoperative day. In 7/17 cases of PMT the pleural space was opened and drained. Mean operation time (incl. waiting period for intraoperative frozen section and complete resection in a few cases) was 77 (45-100) min for VT, 49 (10-180) min for PMT and 41 (20-105) min for CM. Histological diagnosis of biopsy specimens were conclusive in all VT cases, in 15/17 PMT (88%) and in 37/42 CM (88%). Two major complications occurred: one recurrent nerve palsy following VT-resection of a neurinoma originating from the recurrent nerve itself; in a second patient submitted to mediastinoscopic biopsy, venous bleeding had to be managed by surgical sternotomy. CM as the most approved method for paratracheal and anterior subcarinal biopsies has not lost its importance. PMT as a simple and usually extrapleural intervention can further be advocated for anterior mediastinal lesions. VT turns out to be rather a complementary than a competitive invasive mediastinal diagnostic procedure and is regarded as method of choice for diagnostic approach to posterior, posterior subcarinal and aorticopulmonary lesions.