Background: Acute liver failure (ALF) is a critical illness with a large number of viral and nonviral causes. Clinical course and etiologies in the Asian countries are different from those reported from the Western world and mortality is high. There may even be intracountry variations in large countries like India, which have differing culture, ethnicity, and environment. Data from North-east part of India is lacking. Materials and methods: Acute liver failure cases (>14 years of age) seen over a period of 8 years (n = 255) were studied at a Government Medical College in Assam for their etiological and other demographic profile. Viral serology was carried out and revalidated at a laboratory in New Delhi. Results: Majority of cases were <30 years of age. Commonest etiology was nonviral (non-ABCE). Amongst viral causes, hepatitis A and E were common, while hepatitis B virus (HBV) was rare. Unknown herbal medication use was very frequent in our cases with a significantly higher mortality. Mortality was highest in cases in 3rd decade of life. Statistically, international normalized ratio (INR) was the strongest predictor of death. Conclusion: Unlike the rest of India, hepatitis virus is not the major cause of ALF in our part; hepatitis A being commoner than hepatitis E, and B is rare. Unknown herbal medications are major cause of mortality and is important medicosocial issue. Our study highlights the differences in the profile of ALF from other Indian and western studies, possibly due to sociocultural factors prevalent in this part.