Infections with the zoonotic liver flukes Fasciola gigantica and Fasciola hepatica may result in severe disease in humans. In Vietnam, an emergence of fascioliasis cases has been observed from the late 1990s onwards. Various diagnostic tools are used in the country, but the agreement between these tools has not been critically evaluated. We aimed to describe the clinical presentation and diagnostic outcomes in fascioliasis patients in Vietnam. A retrospective, cross-sectional study was conducted on the medical records of a group of 145 patients diagnosed with fascioliasis at a tertiary referral hospital in Hanoi. Based on the review, sociodemographic background and clinical presentation were recorded. These patients all received standard routine serologic tests, including internal antibody (Ab)-ELISA, an enzyme-linked immunosorbent assay (ELISA), and commercial coproantigen (cAg)-ELISA. The majority of cases were between 30 and 59 years old (68.3%), and about half of them were male (51.0%). Upper quadrant and epigastric pain were the most commonly reported symptoms (61.4% and 35.2%, respectively). All but one patient had liver lesions upon ultrasound examination (99.3%), and eosinophilia was present in most of the patients (89.7%). A high number of patients were positive in the in-house and the commercial Ab-ELISA (95.9% and 87.4%, respectively), yet only a slight agreement was observed between the two tests (kappa coefficient, 0.06). A further 47.4% of cases were positive for the commercial cAg-ELISA, whereas stool microscopy indicated the presence of Fasciola spp. eggs in 25.7% of patients. The current study emphasizes the challenges related to the diagnosis of human fascioliasis in Vietnam.