We sought to evaluate the safety and efficacy of Amplatzer septal occluder (ASO) to close very large pulmonary arteriovenous fistula (PAVF). Transcatheter coil embolization, the standard treatment for PAVF, has potential complications particularly in patients with very large fistulas. Several recently available devices have been tried effectively, however, they too have limitations. During 2004, three patients (aged 17-56 years), diagnosed with large PAVF including one with pulmonary artery (PA) to left atrial (LA) fistula, had interventional closure prospectively using ASO. Following hemodynamic evaluation and angiographic localization of PAVF, the feeding artery (FA) was selectively cannulated with Amplatzer delivery sheath. ASO, with the right atrial (RA) disc diameter equal to or up to 4 mm larger than the maximum diameter of FA, was delivered through it in such a way that the left atrial disc assumed an oblong shape and the right atrial disc retained its designed flat configuration for better anchorage and thrombogenicity. All patients had very large PAVF fed by a single FA (size 12-24 mm), which was closed completely, without complications, using ASO (size 7-16 mm; RA disc diameter 15-26 mm). Their arterial saturation rose from mean 72.3% to 97.3%. Follow up (1.5-3 years) showed disappearance of the radiological shadows and stable arterial saturations (mean 97.7%). We conclude that, using the new criteria for device size selection and modified technique of implantation, very large PAVFs including PA to LA fistula can be closed safely, effectively and nonsurgically with ASO.