Sudden cardiac death is the most common cause of death from heart failure. The sodium-calcium exchanger 1 (NCX1) is predominantly expressed in the heart. Several studies have reported that cardiac NCX1 is overexpressed and/or activated in human end-stage and experimental heart failure. To investigate the physiological and pathological roles of cardiac NCX1, we generated tamoxifen-inducible cardiac-specific NCX1 knockout (cNCX1^-/-) mice. We found that cNCX1^-/- mice died suddenly within a week after the induction of conditional gene deletion. In this study, we analyzed in vivo the characteristics of sudden death in cNCX1^-/- mice. cNCX1^-/- mice exhibited lower systemic blood pressure and LV fractional shortening than control mice. In heart tissue from cNCX1^-/- mice, furthermore cardiac hypertrophy and myocardial fibrosis occurred. Electrocardiographic analysis using telemetry system revealed that cNCX1^-/- mice exhibited a marked decrease in heart rate, prolongation of RR interval and short QTc. Intriguingly, characteristic QT prolongation and ventricular fibrillation were observed just before the sudden cardiac death of cNCX1^-/- mice. These results suggest that cardiac NCX1 has an essential role for the maintenance of cardiac structure and function in mice.