Abstract Background The arterial switch operation (ASO) is the current technique of choice for the repair of the transposition of the great arteries (d-TGA). Its main advantage is that the left ventricle (LV) sustains the systemic circulation, thus diminishing the risk of late systolic dysfunction as seen in the atrial switch technique. Purpose To study the systolic LV performance in a large cohort of adult patients after ASO and to explore clinical determinants of reduced left ventricular systolic function (LVSF). Methods EPOCH-ASO is an ongoing prospective, multicentre, international cohort study involving 11 reference centres from 5 different countries, that includes adult d-TGA patients after ASO. We conducted a cross-sectional analysis of clinical and echocardiographic data from all patients enrolled in EPOCH-ASO. LVSF was considered reduced when ejection fraction (EF) by Simpson’s method was < 54% in women or <52% in men, or by visual assessment when EF could not be obtained. Results 513 patients have been included in EPOCH-ASO, with a median age of 25.3 years [IQR: 21 – 28 years] at the time of enrolment. At baseline, 41% had history of at least one reintervention (23.2% at the right ventricular outflow tract (RVOT), 5.1% at the left ventricular outflow tract (LVOT), 4.5% at the aortic arch, 3.3% pacemaker implantation). Echocardiographic data were obtained in 450 patients (88 % of the total cohort). Left ventricular ejection fraction (LVEF) by biplane Simpson method was available in 316 patients (mean LVEF 58.3 ± 7.2%), while visual assessment of LVSF was performed in 134 patients. For the total cohort with echocardiographic data available, 62 (13.8%) had a reduced LVSF. Global longitudinal strain (GLS) analysis was available in 145 patients (28.2% of the total cohort), with a mean value of -17.4% ±2.7%. GLS was impaired (>-18%) in 53% of the patients. Furthermore, 48% of the 117 patients with normal LVEF had a reduced GLS. Older age at the time of the echocardiography, late repair (>12th day), a previous pulmonary banding or having a pacemaker implanted were factors associated with an impaired LVSF. In the multivariate analysis, age at the time of the echocardiography (OR 1.06 per year, CI 1.01-1.12; p<0.001) and late repair (OR 1.85, CI 1.11-3.06, p=0.03) remained significant. As for the speckle tracking analysis, a significantly lower GLS was found in patients after LVOT intervention (-15% vs -17.6%, p=0.005) and with a neo-aortic root above the median (37.5 mm) (GLS -17% vs -18%, p=0.03). In the multivariate analysis only LVOT intervention remained significant (p=0.016). Conclusions Left ventricular systolic dysfunction is not exceptional in patients after ASO and it may become a concern as this population ages. Speckle tracking analysis might identify earlier stages of ventricular dysfunction. Large comprehensive longitudinal studies are needed to better characterize the left ventricular systolic function in this patient population.