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Background: The outcomes, complications, and rates of secondary malignancies from radiation therapy (RT) are not known for patients with familial adenomatous polyposis (FAP). Methods: We queried the Hereditary Gastrointestinal Cancer Registry (HGCR) for patients with FAP who received RT. Outcomes assessed included acute and late treatment toxicity and secondary malignancies. Results: We identified 15 patients undergoing 18 treatment courses. Median follow-up was 3.1 years after RT. Treated sites included rectal cancer, desmoid, prostate cancer, breast cancer, melanoma, medulloblastoma, gastric cancer, and glioma. Secondary tumors occurred in two patients: a medulloblastoma was diagnosed in a patient treated for glioma, and a desmoid tumor was diagnosed in a patient treated for rectal cancer. All nine patients treated with intra-abdominal or pelvic RT had prior prophylactic proctocolectomies, yet only one patient experienced grade 3 gastrointestinal toxicity. Common Terminology Criteria for Adverse Events version 4 (CTCAE v4) toxicities were grade 1 in seven treatment courses (39%), grade 2 in five courses (28%), and grade 3 in two courses (11%). Conclusions: In this cohort, RT was well tolerated with adverse effects comparable with non-FAP patients. Secondary in-field tumors occurred in 2 of 15 patients and their increased risk in this cohort was likely due to prior predilection from FAP itself, although an increased role of RT cannot be ruled out.