Background and objectives. Angiographic assessment of the severity of intermediate lesions in the left main coronary artery (LMCA) is subject to significant limitations. Intravascular ultrasound (IVUS) can provide accurate measurement, but there is no agreement on the minimum lumen cross-sectional area (MLA) that indicates significant disease. The aim of this study was to determine the longterm safety of applying a cut-off value of 6 mm(2) for the MLA in the LMCA. Methods. The study included patients with intermediate lesions (i.e., 25-50%) in unprotected LMCAs, with no previous evidence of associated ischemia. An IVUS examination was carried out and revascularization was indicated when the MLAwas <= 6 mm(2). Results. In total, 79 patients were recruited between 2000-2005. In 31 (39%), the MLA was <= 6 mm(2), and they underwent LMCA revascularization; in the remaining 48 (61%), the MLA was > 6 mm(2), and patients either underwent angioplasty for other lesions (n=37) or continued medical treatment (n=11). In a follow-up period of 40 [17] months, four patients (8.3%) died from heart disease, all of whom had an MLA between 9-10 mm(2) in the baseline study. Revascularization of the LMCA was necessary in only two patients (4.2%), both of whom had elective surgery more than 2 years after the initial study. Conclusions. Intravascular ultrasound assessment of intermediate LMCA lesions using an MLA cut-off value of 6 mm(2) appears safe over the long term provided the clinical and angiographic criteria applied to patient selection are similar to those used in this study.