Objective To investigate the risk factors for multiple organ failure in the elderly (MOFE). Methods A total of 656 patients who were admitted to the geriatric, cardiovascular, neurological and gastroenterological departments and intensive care unit of our hospital from January 2013 to February 2016 were enrolled in this study. They were divided into MOFE group (n=280) and non-MOFE group (n=376). Their general information, clinical data and comorbidity of chronic diseases were collected and surveyed. Stepwise logistic regression analysis was used to screen the independent risk factors for MOFE. Results Before the onset, the MOFE patients had at least ≥2 kinds of chronic diseases. Chronic heart failure, chronic respiratory failure, cerebrovascular disease, renal insufficiency and diabetes mellitus were independent risk factors for MOFE. Conclusion Chronic underlying disease is an important pathological basis of MOFE. For the patients who have above risk factors, the treatment to chronic underlying diseases need to be strengthened to actively protect and improve the function of viscera, so as to prevent the occurrence and mortality of MOFE.