Objective.  To determine the causes and outcome of all patients with acute liver failure (ALF) in Sweden 1994–2003 and study the diagnostic accuracy of King's College Hospital (KCH) criteria and the model for end‐stage liver disease (MELD) score with transplant‐free deaths as a positive outcome.

Research design and methods.  Adult patients in Sweden with international normalized ratio (INR) of ≥1.5 due to severe liver injury with and without encephalopathy at admission between 1994–2003 were included.

Results.  A total of 279 patients were identified. The most common cause of ALF were acetaminophen toxicity in 42% and other drugs in 15%. In 31 cases (11%) no definite etiology could be established. The KCH criteria had a positive‐predictive value (PPV) of 67%, negative‐predictive value (NPV) of 84% in the acetaminophen group. Positive‐predictive value and negative‐predictive value of KCH criteria in the nonacetaminophen group were 54% and 63% respectively. MELD score >30 had a positive‐predictive value of 21%, negative‐predictive value of 94% in the acetaminophen group. The corresponding figures for the nonacetaminophen group were 64% and 76% respectively.

Conclusions.  Acetaminophen toxicity was the most common cause in unselected patients with ALF in Sweden. KCH criteria had a high NPV in the acetaminophen group, and in combination with MELD score <30 predicts a good prognosis in acetaminophen patients without transplantation.