Background: Targeted therapy for actionable mutations in advanced cholangiocarcinoma (CCA) has revolutionized second and third-line treatment algorithms. Their application in early stage disease is not defined. The incidence and prognostic value of actionable mutations in pts with early stage resected disease is not known. Methods: The Cholangiocarcinoma Foundation and Ciitizen (a wholly owned subsidiary of Invitae Corporation) collaboratively launched a registry platform that directly consents pts and collects comprehensive medical records. Presently, de-identified data including clinical characteristics, molecular testing, interventions, and outcomes have been extracted and standardized for research use on 400 pts. The data is longitudinal with regularly planned updates. We identified pts who underwent resection of non-metastatic disease and underwent genetic testing. Actionable mutations recorded included FGFR2 fusion/rearrangement, IDH1 mutation, HER2 amplification, BRAF mutation, MSI-high, and TMB-high. Primary outcome was recurrence-free survival (RFS). Results: Of 400 pts, 137 underwent resection for CCA. When compared to pts with advanced disease, those who underwent resection had a similar frequency of genetic testing and presence of actionable mutations: 94.3% (n=248) vs 83.9% (n=115) and 38.7% (n=96) vs. 33.0% (n=38), respectively. When considering pts with non-metastatic, resected disease who underwent molecular testing (n=104), the mean age was 59.2 yrs, 66 (63.5%) were females, and 60 (57.7%) had intrahepatic cholangiocarcinoma (iCCA), 42 (40.4%) had extrahepatic disease, and 2 (1.9%) were not otherwise specified. The majority received molecular testing before or at the time of surgery (n=89, 85.6%). Of pts with non-metastatic resectable disease who received genetic testing, 34 pts (32.7%) had actionable mutations: FGFR2: n=7 (6.7%), IDH1: n=16 (15.4%), HER2: n=5 (4.8%), BRAF: n=0 (0%), MSI-high: n=3 (2.9%), TMB-high: n=8 (7.7%). FGFR2 fusion/rearrangement and IDH1 mutations were only identified in iCCA. Pts with an FGFR2 fusion/rearrangement were younger (49.9 vs 59.8 yrs; p=0.03) and all were female. Although not statistically significant, the presence of an FGFR2 fusion/rearrangement was associated with nearly a doubling of median RFS (32.0 vs 17.3 mos; p=0.19) for patients with iCCA. Conclusions: In this highly selected cohort of pts with resected, early stage, non-metastatic CCA, the majority underwent molecular profiling before or at the time of surgery. As expected, FGFR2 fusion/rearrangement and IDH1 mutations were only present in iCCA. An FGFR2 fusion/rearrangement was seen in young, female pts and may have a favorable prognostic value as suggested by a trend in increased RFS. Clinical trials are needed to assess the value of administering targeted therapy to this patient population in the adjuvant or neoadjuvant setting.