The major determinant of prognosis in cases of hereditary hemochromatosis (HH) is the degree of organ damage from iron overload at the point of diagnosis. The presence of liver cirrhosis reduces life expectancy. Damage that has occurred to tissues and organs is irreversible, but further damage can be halted with treatment. When there is no evidence of cirrhosis at time of diagnosis, life expectancy may be equal to that of persons without HH. With proper management of HH through treatment, affected individuals have good long-term outcomes.

Hepatocellular carcinoma associated with cirrhosis, hepatic failure, and cardiac failure are the most common causes of death in persons with HH. Compared to the normal population, liver cancer is many times more prevalent as a cause of death in persons with HH. Cardiomyopathy, diabetes, and cirrhosis are all more common causes of death among persons with HH than among normal persons. The earlier HH is detected, before the onset of severe organ damage, the lower the risk of mortality.