PURPOSE: As the number of cancer survivors in the United States increases, quantifying the risks and burden of second primary cancers (SPCs) among cancer survivors will help develop long-term prevention and surveillance strategies. We describe the risk of developing a SPC among survivors of 10 cancer sites with the highest survival rates in the United States. METHODS: Adult patients diagnosed with an index smoking-related (urinary bladder, kidney and renal pelvis, uterine cervix, oral cavity and pharynx, and colon and rectum) and index non-smoking-related (prostate, thyroid, breast, corpus and uterus, and non-Hodgkin lymphoma) cancers were identified from Surveillance, Epidemiology, and End Results (2000-2015). SPC risks were quantified using standardized incidence ratios (SIRs) and excess absolute risks (EARs) per 10,000 person-years at risk (PYR). RESULTS: A cohort of 2,903,241 patients was identified and 259,685 (8.9%) developed SPC (7.6% of women and 10.3% of men). All index cancer sites (except prostate) were associated with a significant increase in SPC risk for women and men. Patients diagnosed with smoking-related index cancers (SIR range 1.20-2.16 for women and 1.12-1.91 for men) had a higher increased risk of SPC than patients with non-smoking-related index cancers (SIR range 1.08-1.39 for women and 1.23-1.38 for men) relative to the general population. CONCLUSION: We found that 1-in-11 cancer survivors developed a SPC. Given the increasing number of cancer survivors and the importance of SPC as a cause of cancer death, there is a need for increased screening for and prevention of SPC.