Background: Cirrhosis remains the most frequent liver-related cause of death worldwide and we aimed to evaluate its burden in Brazil from 2000 to 2012. Material and methods: The Brazilian National Death Registry was analyzed from 2000 to 2012. Death by cirrhosis was defined by the presence of I85, K73 and/or K74 ICD 10 codes in contributing or underlying causes of death on the death certificate (DC). Crude mortality rates were calculated as the ratio of the absolute number of deaths and the estimated population. Mortality rates were age-adjusted by the direct standardization method using the WHO standard population. Results: A total of 265,180 deaths where cirrhosis was mentioned on the DC [77% male, aged 56 years] occurred from 2000 to 2012. Cirrhosis codes were present in 46% of liver-related deaths and 2% of all deaths in this period. Despite an increase in the absolute number of deaths (n = 18,245 to 22,340), the age-standardized mortality rates (95%CI) decreased from 13.32 (13.16-13.48) to 11.71 (11.59-11.83) per 100,000 inhabitants from 2000 to 2012 (p < 0.001). This trend was not uniform across the country, with decreases in death rates in the South [14.46 (14.07-14.87) to 10.89 (10.59-11.19)] and Southeast [15.85 (15.6-16.09) to 12.52 (12.34-12.70)] and increases in the North [8.84 (8.24-9.43) to 11.53 (11.08-11.99)] and Northeast [9.41 (9.13-9.69) to 10.93 (10.68-11.17)] (p < 0.001 for all). Conclusion: Cirrhosis remains a major public health issue, despite the reduction in mortality rates in the last decade.