Background: Data needed to develop age-appropriate survivorship care guidelines for AYA cancer are lacking. Using a retrospective cohort design, we described risk of chronic comorbidities in AYA cancer survivors. Methods: 6,778 two-year survivors of cancers diagnosed at age 15-39y at Kaiser Permanente Southern California between 2000-2012 were included. A non-cancer comparison group (N = 87,737) was matched to cancer survivors (1:13) on age, sex and calendar year. New onset of comorbidities listed in Table 1 was ascertained using ICD-9 diagnosis codes, laboratory values, medication prescription and cause of death in the electronic health records through end of 2014. Incidence rate and incidence rate ratio (IRR) from Poisson regression adjusting for age, sex, race/ethnicity were derived for each comorbidity. Within cancer survivors, multivariable Poisson regression was used to evaluate the associations between chemotherapy exposures (mutually adjusted) and risk of selected comorbidities. Results: Median age at cancer diagnosis was 33y; 35% were male; 42% were non-Hispanic white. The most common cancer types were thyroid (16%), breast (16%) and melanoma (10%). Comparison with non-cancer subjects: see Table 1. Within cancer survivors: chemotherapy exposure was associated with multiple comorbidities. The largest IRR was found for methotrexate use and avascular necrosis (AN) (IRR = 15.5); followed by ifosfamide and chronic kidney disease (IRR = 8.3); and bleomycin and pulmonary fibrosis (IRR = 4.7). Conclusions: These data provide basis for identifying high-risk individuals for population-based targeted surveillance.