BACKGROUND: The risk of developing strongyloidiasis hyperinfection syndrome appears to be elevated among individuals who initiate corticosteroid treatment. Presumptive treatment or treatment after screening for populations from Strongyloides stercoralis-endemic areas has been suggested before initiating corticosteroids. However, potential clinical and economic impacts of preventative strategies have not been evaluated. METHODS: Using a decision tree model for a hypothetical cohort of 1000 individuals from S. stercoralis-endemic areas globally initiating corticosteroid treatment, we evaluated the clinical and economic impacts of two interventions, 'Screen and Treat' (i.e. screening and ivermectin treatment after a positive test), and 'Presumptively Treat', compared to current practice (i.e. 'No Intervention'). We evaluated the cost-effectiveness (net cost per death averted) of each strategy using broad ranges of pre-intervention prevalence and hospitalization rates for chronic strongyloidiasis patients initiating corticosteroid treatment. RESULTS: For the baseline parameter estimates, 'Presumptively Treat' was cost-effective (i.e. clinically superior with cost per death averted less than a threshold of $10.6 million per life) compared to 'No Intervention' ($532 000 per death averted) or 'Screen and Treat' ($39 000 per death averted). The two parameters contributing the most uncertainty to the analysis were the hospitalization rate for individuals with chronic strongyloidiasis who initiate corticosteroids (baseline 0.166%) and prevalence of chronic strongyloidiasis (baseline 17.3%) according to a series of one-way sensitivity analyses. For hospitalization rates ≥ 0.022%, 'Presumptively Treat' would remain cost-effective. Similarly, 'Presumptively Treat' remained preferred at prevalence rates of ≥ 4%; 'Screen and Treat' was preferred for prevalence between 2 and 4% and 'No Intervention' was preferred for prevalence <2%. CONCLUSIONS: The findings support decision-making for interventions for populations from S. stercoralis-endemic areas before initiating corticosteroid treatment. Although some input parameters are highly uncertain and prevalence varies across endemic countries, 'Presumptively Treat' would likely be preferred across a range for many populations, given plausible parameters.