The clinical effectiveness and safety of balloon atrioseptostomy (BAS) under color flow mapping Doppler echocardiography (CFM) guidance was evaluated in 21 BAS procedures performed on 19 patients with cyanotic heart disease (d-TGA 15, PA 1, TA 2, Ebstein's anomaly PA + supramitral ring 1) in the cardiac catheterization laboratory (16 patients) or in the intensive care unit (ICU 3 patients). The indication for BAS was established based on CFM diagnosis. BAS was performed with combined CFM and X-ray guidance on 16 patients prior to cardiac catheterization, and with CFM guidance only on 3 patients in the ICU. A series of BAS was performed until satisfactory interatrial opening was obtained and a complete hemodynamic study was performed by CFM and catheterization after BAS, if possible. In all 19 patients BAS was performed very safely with positioning of balloon in the left atrium, selection of appropriate size of balloon, and the confirmation of the effect of BAS provided by CFM guidance at each step. The size of the interatrial opening was significantly increased from 2.6 to 8.1 mm (p < 0.01) after a series of BAS and the arterial oxygen saturation was significantly increased from 44 to 75% (p < 0.01). CFM provides effective diagnosis and guidance for BAS in severely cyanotic neonates with congenital heart disease, and should significantly contribute to the speed, efficacy, and safety of the procedure.