Abstract Background Currently, Chagas disease (CD) is widespread in European nations that host notable populations from Latin America. Vertical transmission is a pathway for the spread of the disease in countries where it is not endemic. Due to socio-economic disparities, CD is a public health concern in non-endemic regions, raised by migration phenomena in vulnerable population groups who face similar hindrances as those most at risk in endemic areas. The aim is to evaluate the cost-effectiveness of CD screening versus no screening in pregnant women and their infants in Italy. Methods A Bayesian Markov model was employed to compare the CD screening versus the no screening alternative. Model parameters were sourced from pertinent scientific literature. A lifetime perspective was adopted, aligning with the perspective of the Italian National Health Service. The Eurozone threshold was applied. Costs and benefits were discounted at a rate of 3%. Gibbs sampling served as the algorithm for Bayesian inference. Uncertainty was addressed through a probabilistic sensitivity analysis (PSA) and a value of information analysis (VOI), depicted via the Cost-Effectiveness Acceptability Curve (CEAC) and Expected Value of Perfect Information (EVPI). Results were presented as the Incremental Cost-Effectiveness Ratio (ICER). Results The base case results showed that CD screening was cost-effective, with an ICER of €5,112 [€1,850 - €10,043]. Furthermore, according to the CEAC, the screening option exhibited the greatest probability of being cost-effective across all thresholds. Additionally, the EVPI per mother was €818 based on a threshold of €50,000/diagnosis. Conclusions Implementing a structured CD screening program also in non-endemic countries has the potential for early detection and treatment. This contributes to SDG 3 by improving access to healthcare, preventing transmission, and reducing the disease burden as well as informing public health policies for marginalised populations. Key messages • This study proves that screening for CD in pregnant women and their infants in a non-endemic area is a cost-effective strategy and possibly cost-saving in the long term. • Study findings could support a wider implementation of CD screening in Italy by informing health policy-makers in their decision-making process.