Background Cholangiocarcinoma (CCA) represents a global health challenge, with rising incidence and mortality rates. This study aimed to elucidate the clinical course and practices of CCA in Latin America. Methods This observational cohort study investigated individuals diagnosed with CCA between 2010 and 2023 at fi ve referral centres across Latin America. Demographic, biochemical, and clinical data were analysed. Findings A total of 309 patients were enrolled, demonstrating a balanced distribution of CCA subtypes (intrahepatic, perihilar, and distal), with Hispanics and Caucasians as the predominant ethnic groups, followed by Africans. Major risk factors identified included age, diabetes, obesity, MASLD, bile duct stones, and cholecystitis. Disparities in overweight/obesity prevalence were noted among CCA subtypes and ethnicities, with higher rates in extrahepatic CCA and among Hispanics and Caucasians. At diagnosis, 72% of patients had ECOG-PS scores of 0-1, with disease presentations ranging from localized (47%) to locally advanced (19%) and metastatic (34%). Patients who did not receive any anti-cancer therapy exhibited a median survival of 2.3 months. Survival rates significantly improved across treatment modalities, with surgery yielding the longest (34 months), followed by chemotherapy (8 months). Notably, Africans presented with worse ECOG-PS scores and more advanced disease, while Hispanics were less frequently treated with chemotherapy for advanced disease, contributing to lower survival rates (8.3 and 6 months, respectively) compared to Caucasians (12.6 months). Interpretation The high prevalence of late-stage CCA diagnosis in Latin America, particularly among individuals of African ethnicity, coupled with a significant proportion of Hispanic patients not receiving chemotherapy, underscores the dismal prognosis for these patients. These fi ndings reveal structural challenges in cancer screening and healthcare access among diverse ethnic backgrounds and lower socioeconomic statuses in the region. Urgent measures are needed, including the identification of preventable risk factors, raising awareness among high-risk populations, and establishing equitable health coverage to address these disparities.