BACKGROUND Pre-excitation cardiomyopathy is a specific type of cardiac disease related to asymptomatic pre-excitation. It is rarely reported and is prone to misdiagnosis; therefore, the actual incidence of pre-excitation cardiomyopathy may be underestimated. The purpose of this case report is to present a case of pre-excitation cardiomyopathy caused by an accessory pathway. CASE REPORT A 25-year-old woman was admitted to the hospital with concerns of recurrent chest tightness and decreased exercise tolerance for 3 months. Pre-excitation was found by electrocardiogram. Contraction of the left ventricular wall reduced diffusely, and the overall left ventricle moved asynchronously. The regional septum basal segment swung to the right ventricle like an aneurysm in systolic period. No significant myocardial fibrosis was found. Pathological examination of endomyocardial biopsy demonstrated nonspecific changes of mild interstitial edema. Pre-excitation cardiomyopathy was eventually diagnosed. A right anteroseptal para-hisian manifest accessory pathway was located in an electrophysiological study, and radiofrequency catheter ablation was subsequently performed to block the advanced conduction. During the follow-up at 6 months after ablation, left ventricular dyssynchrony and systolic dysfunction were improved and symptoms were significantly relieved. CONCLUSIONS Pre-excitation cardiomyopathy is characterized by asynchronous left ventricular motion, impaired cardiac function, and manifestations of heart failure. Asynchronous electromechanical contraction coupling plays an essential role in the pathogenesis. Blocking the accessory pathway could help to correct the dyssynchrony, reverse remodeling, improve left ventricular function, and alleviate symptoms. Patients can have a good prognosis through accurate diagnosis and appropriate treatment.