Background: Biliary tract cancer (BTC) is a heterogeneous group of tumours, including cholangiocarcinoma (intrahepatic and extrahepatic) and gallbladder carcinoma (GC). With this work, we aim to perform an epidemiological characterization of patients with BTC, their management and survival outcomes from a nationwide registry in Spain. Methods: We performed an epidemiologic analysis of a cohort of patients from the Spanish RETUD registry diagnosed with BTC between 1 January 2017 and 31 December 2020. Data collected included sociodemographic and clinical outcomes, molecular analysis, oncological treatments, and survival. Patients with all the aforementioned data available on the cut-off date of 7 July 2021 were considered in the analysis. It included descriptive statistics of patient characteristics, tumour molecular markers and treatments. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results: A total of 778 evaluable patients were included in 19 sites, with a median (interquartile range, IQR) age of 72.2 (64.5-78.5) years, 54.8% men. At primary diagnosis, the tumour was mostly intrahepatic (57.2%); followed by extrahepatic (27.4%) and GC (13.8%) and histologically diagnosed (83.7%). Most of the patients has advanced disease at diagnosis (72.0%). At database cut-off, the disease was metastatic in 525 (67.5%) patients, and the main metastatic sites were the liver n = 333 (63.4%), lymph distant nodes n = 187 (35.6%) and peritoneum n = 175 (33.3%). Any biomarker analysis was done in 245 (31.5%) patients whose main findings were: IDH1 mutations (n = 33, 17.7%), FGFR2 fusions (n = 15, 8.4%), BRAFV600E mutation (n = 10, 5.7%), MSI (n = 14, 6.8%) and HER2 amplification (n = 5, 3.0%). Previous surgeries were reported in 261 (33.5%) patients, and systemic oncologic therapies in 586 (75.3%): neoadjuvant n = 11 (1.9%), adjuvant n = 135 (23.0%), first line n = 549 (93.7%), second line n = 237 (40.4%), and third line and beyond n = 113 (19.3%). The main first-line treatment was cisplatin/gemcitabine (CISGEM; n = 331, 64.4%), followed by gemcitabine monotherapy (n = 100, 19.5%) and gemcitabine plus oxaliplatin (GEMOX; n = 48, 9.3%). The median (95% CI) PFS from first line in patients exposed to CISGEM was 5.1 (4.6-5.8) months. The median OS in metastatic population (95% CI) was 8.3 (7.2-9.1) months. Conclusions: This analysis provides insights into the characterization of BTC, its therapeutic management and clinical outcomes in Spanish sample patients. Obtained data are consistent with the published literature; nevertheless, we must consider them in the context of a currently evolving scenario. Although molecular analysis has gained relevance, it is still poorly performed in daily practice in Spain.