BACKGROUND: Primary graft dysfunction remains the leading cause of 30-day mortality after heart transplantation. Few data have been published about the clinical outcome of severe primary graft dysfunction treated with venoarterial extracorporeal membrane oxygenation (VA-ECMO). AIM: To evaluate the prevalence and outcome of severe primary graft dysfunction requiring VA-ECMO, and to identify factors associated with hospital mortality. METHODS: We performed an observational analysis of our institutional database of VA-ECMO for primary graft dysfunction after heart transplantation. Patients with severe primary graft dysfunction, according to the International Society for Heart and Lung Transplantation classification, were included. The primary outcome was survival to hospital discharge. Risk factors for in-hospital mortality were searched with multiple logistic regression analysis using backward stepwise variable elimination. RESULTS: Of the 397 patients who had heart transplantation between January 2007 and December 2018, 60 (15.1%) developed severe primary graft dysfunction requiring VA-ECMO. The median age was 52 (interquartile range 39-59) years, and 73.3% were male. Thirty-nine (65.0%) patients were weaned after a mean duration of VA-ECMO support of 7.2±6.0 days. Thirty-two (53.3%) patients were alive at hospital discharge. Inotropic support in the recipient before heart transplantation (odds ratio [OR] 3.88, 95% confidence interval [CI] 1.04-14.44; P=0.04), total ischaemic time (OR 0.99, 95% CI 0.99-1.00; P=0.01) and 48-hour total blood transfusion (OR 1.14, 95% CI 1.04-1.26; P=0.01) were independent predictors of in-hospital mortality. CONCLUSIONS: Severe primary graft dysfunction requiring VA-ECMO is frequent after heart transplantation. Survival to hospital discharge after VA-ECMO for severe primary graft dysfunction is satisfactory in such a critically ill population.