Despite the rising incidence of obesity and diabetes, there is little emphasis on morbidity and mortality from obesity-related cirrhosis, usually considered a rare and asymptomatic condition. Our aim was to assess survival and the occurrence of hepatocellular carcinoma and complications of hepatic insufficiency in obesity-related cryptogenic cirrhosis compared with cirrhosis of other origins. We analyzed retrospectively 27 overweight patients with cryptogenic cirrhosis (CC-O), 10 lean patients with cryptogenic cirrhosis (CC-L) and 391 patients with hepatitis C virus-related cirrhosis (C-HCV). In CC-O patients, cirrhosis was detected later in life than in C-HCV and CC-L patients. Severe liver disease was as frequent in CC-O as in C-HCV patients as indicated by the proportion of Child B or C or of episodes of hepatic decompensation. Survival of CC-O patients was lower than that of untreated, age- and sex-matched C-HCV controls (P < .02 at 30 months), with a higher mortality of Child B or C patients. Hepatocellular carcinoma was detected in 8 of 27 (27%) CC-O patients versus 21% of matched C-HCV controls with a similar age cumulated incidence, suggesting a comparable carcinogenic potential. In conclusion, obesity-related cirrhosis should now be recognized as a distinct entity that can cause severe liver disease and death. Increased awareness of and better diagnostic strategies for nonalcoholic steatohepatitis in overweight patients are urgently needed.