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Introduction Acute liver failure (ALF) is a syndrome defined by jaundice, coagulopathy (INR > 1.5) and hepatic encephalopathy in patients with no evidence of prior liver disease. Toxins and drugs are a frequent cause of ALF in children. Material and methods The aim of our study was to establish the causes of toxic ALF in children followed up in our hospital in the period of January 2000 to August 2018. We retrospectively studied all hospital records of patients who developed ALF after mushroom/drug exposure and had been admitted to our hospital, the main pediatric toxicology center in north-western Romania. Results In the last 18 years, 123 patients were admitted to our clinic with toxic ALF (89 patients secondary to mushroom ingestion and 34 patients after drug exposure). In the 2000-2012 period accidental mushroom poisoning was the leading cause of toxic ALF. Unfortunately, during the last years, voluntary drug ingestions have increased dramatically. The most commonly incriminated drug was acetaminophen (52.94%). Conclusions ALF in mushroom poisoning is associated with a high mortality in children, despite optimal medical therapy. This etiology was one of the most important causes of death in our cohort. The difficulty in accessing emergency liver transplantation is an obstacle common to many Eastern European pediatric centers. Fortunately, in the last 5 years the incidence of mushroom intoxications has decreased in our area. It is worrying that over the last few years there has been an increased incidence of toxic ALF after drug exposure (for suicidal purposes or due to lenient regulations for prescribing hepatotoxic medications).