The severity of cystic fibrosis varies greatly from person to person regardless of age; the severity is determined largely by how much the lungs are affected. In the United States, half of the people with cystic fibrosis live about 33 years or longer. The outlook for longer survival has improved steadily over the past 50 years, mainly because treatments can now postpone some of the changes that occur in the lungs. Long-term survival is somewhat better in males and in people whose initial symptoms were restricted to the digestive tract; however, long-term survival is also significantly better in people who do not develop pancreatic problems.

However, deterioration is inevitable, leading to loss of lung function and eventually death. People with cystic fibrosis usually die of respiratory failure after many years of deteriorating lung function. A small number, however, die of heart failure, liver disease, bleeding into the airways, or complications of surgery. Despite their many problems, people with cystic fibrosis usually attend school or work until shortly before death.