ABSTRACT: BACKGROUND:Relative to the general population, cancer patients and survivors may have an elevated risk of mortality from noncancer causes, such as cardiovascular disease and infections, but few studies have examined rates of noncancer mortality among patients diagnosed as adolescents and young adults (AYAs) (ages 15-39 years). METHODS:The Surveillance, Epidemiology, and End Results database was used to identify AYA patients who were diagnosed with a first malignant cancer between 1973 and 2015. Rates of mortality from noncancer causes among AYAs with cancer were compared with those in the general US population using standardized mortality ratios (SMRs), adjusted for age, sex, race, and calendar year. RESULTS:Among 235,541 AYAs with cancer, a total of 12,948 deaths from noncancer causes occurred over 3.1 million total person-years of follow-up. Overall, noncancer mortality was significantly increased among AYAs with cancer relative to the general population (SMR, 1.84; 95% CI, 1.80-1.87). SMRs were particularly elevated for infectious diseases (SMR, 5.13; 95% CI, 4.95-5.32), cardiovascular disease (SMR, 1.55; 95% CI, 1.50-1.60), and renal diseases (SMR, 2.40; 95% CI, 2.12-2.71). These associations persisted for more than 20 years after cancer diagnosis. Cancer types associated with the highest SMRs for all noncancer mortality included leukemias (SMR, 5.26), Hodgkin lymphoma (SMR, 3.12), non-Hodgkin lymphoma (SMR, 6.33), central nervous system tumors (SMR, 3.38), head and neck cancers (SMR, 2.09), and cervical/uterine cancers (SMR, 2.03). CONCLUSIONS:AYAs with cancer have an elevated burden of mortality from noncancer causes that persists many years after cancer diagnosis, highlighting the importance of comprehensive, long-term follow-up care for noncancer conditions throughout survivorship.