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Background: The current study is the first to examine the effectiveness and toxicity of postoperative intensity-modulated radiotherapy (IMRT) in the treatment of intrahepatic cholangiocarcinoma (ICC) abutting the vasculature.Specifically, we aim to assess the role of IMRT in patients with ICC undergoing null-margin (no real resection margin) resection.Methods: Thirty-eight patients with ICC adherent to major blood vessels were included in this retrospective study.Null-margin resection was performed on all patients;14 patients were further treated with IMRT.The median radiation dose delivered was 56.8 Gy (range, 50-60 Gy).The primary endpoints were overall survival (OS) and disease-free survival (DFS).Results: At a median follow-up of 24.6 months, the median OS and DFS of all patients (n=38) were 17.7 months (95% CI, 13.2-22.2) and 9.9 months (95% CI, 2.8-17.0), respectively.Median OS was 21.8 months (95% CI, 15.5-28.1) among the 14 patients in the postoperative IMRT group and 15.0 months (95% CI, 9.2-20.9) among the 24 patients in the surgery-only group (P=0.049).Median DFS was 12.5 months (95% CI, 6.8-18.2) in the postoperative IMRT group and 5.5 months (95% CI, 0.7-12.3) in the surgery-only group (P=0.081).IMRT was well-tolerated.Acute toxicity included one case of Grade 3 leukopenia;late toxicity included one case of asymptomatic duodenal ulcer discovered through endoscopy.Conclusions: The study results suggest that postoperative IMRT is a safe and effective treatment option following null-margin resections of ICC.Larger prospective and randomized trials are necessary to establish postoperative IMRT as a standard practice for the treatment of ICC adherent to major hepatic vessels.