Objective: To explore the safety and efficacy of postoperative adjuvant targeted therapy combined with immunotherapy in patients of biliary tract carcinoma with high-risk factors for recurrence. Methods: A retrospective analysis was performed on the clinical data of 24 patients with biliary tract carcinoma complicated with high-risk factors for recurrence, who underwent surgical resection in the First Affiliated Hospital of Nanjing Medical University from January to December 2023, declined adjuvant chemotherapy, and voluntarily opted for targeted therapy combined with immunotherapy. The clinicopathological characteristics, relapse-free survival(RFS), overall survival(OS), and incidence of adverse events(AE) of the enrolled patients were recorded. Survival analysis was performed using the Kaplan-Meier method, and the Cox proportional hazards regression model was used to analyze the factors affecting RFS. Results: During the follow-up of the 24 patients, 12 patients(50.00%) developed recurrence and 7 patients(29.17%) died. The median RFS was 12 months, and the median OS was not reached. Among them, the median RFS and median OS were not reached in patients with R0 resection and high-risk factors for recurrence, while the median RFS was 8 months and the median OS was not reached in patients with R1 resection. The RFS rate and OS rate of patients with R0 resection and high-risk factors for recurrence were significantly higher than those of patients with R1 resection. Prognostic factor analysis showed that age < 60 years, single tumor, R0 resection, no lymph node metastasis, no vascular invasion, and single high-risk recurrence factor were prognostic factors affecting RFS(all P < 0.05). In terms of safety, the incidence of all-grade AE was 79.17%(19/24), and the incidence of grade 3 AE was 8.33%(2/24). No treatment-related death occurred. Conclusion: Postoperative adjuvant targeted therapy combined with immunotherapy shows certain efficacy and controllable safety in biliary tract carcinoma patients with high-risk factors for recurrence. Age <60 years, single tumor, R0 resection, no lymph node metastasis, no vascular invasion, and single high-risk recurrence factor are prognostic factors affecting RFS in this research.