Summary Background Acute‐on‐chronic liver failure ( ACLF ) is a severe complication of liver cirrhosis associated with excess short‐term mortality rates. Orthotopic liver transplantation ( OLT ) is a potentially life‐saving therapeutic modality for acute‐on‐chronic liver failure patients, but selection of transplant candidates with an acceptable post‐transplant outcome is difficult. Aim To assess the risk of liver transplantation in patients with ACLF , and to determine parameters that predict post‐transplant survival in this patient cohort. Methods We retrospectively analysed all 250 patients with cirrhosis who underwent their first liver transplantation between 2009 and 2014 at our institution, and assessed post‐transplant outcomes. Results Of 250 cirrhotic liver transplant recipients, 98 patients fulfilled the diagnostic criteria for acute‐on‐chronic liver failure in the 3‐month pre‐transplant period. Compared to non‐ ACLF patients, ACLF was associated with significantly higher short‐term morbidity and mortality after liver transplantation (90‐day patient survival 96.1% non‐ ACLF vs 72.4% ACLF patients, P < 0.0001). Clinical improvement in the pre‐transplant period, as defined by recovery of at least one previously failed organ system, was observed in 37 of 98 acute‐on‐chronic liver failure patients, mostly within several days after diagnosis. Most notably, clinical improvement prior to liver transplantation was associated with excellent post‐transplant survival rates that approximated non‐ ACLF transplant recipients. Following the 90‐day post‐transplant period, patient survival and long‐term graft functions were comparable between ACLF and non‐ ACLF liver transplant recipients for up to 5 years. Conclusions Acute‐on‐chronic liver failure predicts adverse outcome after orthotopic liver transplantation. Given the dismal prognosis without transplantation, however, our results indicate that ACLF patients can be transplanted with comparably good outcomes, in particular patients who improve under conservative therapeutic measures.