Nonalcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD) pose an important challenge to current clinical healthcare pathways due to a large number of at-risk patients. Therefore, we aimed to explore the cost-effectiveness of transient elastography (TE) as a screening method to detect liver fibrosis in a primary care pathway.Cost-effectiveness analysis using real-life individual patient data from six independent prospective cohorts (five from Europe and one from Asia). A diagnostic algorithm with conditional inference trees was developed to explore the relationships between liver stiffness, socio-demographics, comorbidities, and hepatic fibrosis, the latter assessed by fibrosis scores (FIB-4, NFS) and liver biopsy in a subset of 352 patients. We compared the incremental cost-effectiveness of a screening strategy against standard of care alongside the numbers needed to screen to diagnose a patient with fibrosis stage ≥F2.The data set encompassed 6,295 participants (mean age 55±12 years, BMI 27±5 kg/m, liver stiffness 5.6±5.0 kPa). A 9.1 kPa TE cut-off provided the best accuracy for the diagnosis of significant fibrosis (≥F2) in general population settings, whereas a threshold of 9.5 kPa was optimal for populations at-risk for alcoholic liver disease. TE with the proposed cut-offs outperformed fibrosis scores in terms of accuracy. Screening with TE was cost-effective with mean incremental cost-effectiveness ratios ranging from 2,570 €/QALY (95% CI 2,456-2,683) for a population at-risk for alcoholic liver disease (age ≥45 years) to 6,217 €/QALY (95% CI 5,832-6,601) in the general population. Overall, there was a 12% chance of TE screening being cost-saving across countries and populations.Screening for liver fibrosis with transient elastography in primary care is a cost-effective intervention for European and Asian populations and may even be cost-saving.The lack of optimized public health screening strategies for the detection of liver fibrosis in adults without known liver disease presents a major healthcare challenge. Analyses from six independent international cohorts with transient elastography measurements based on economic modelling shows that a community-based risk-stratification strategy for alcoholic and non-alcoholic fatty liver diseases is cost-effective through earlier identification of patients and potentially cost-saving for our healthcare systems.