Purpose.To develop a general setting–independent decision-analytical model that determines the costs, effectiveness, and cost-effectiveness of four screening strategies to detect amblyopia or amblyogenic factors in pre-school children and to apply the model in a German setting.Methods.The general setting–independent decision–analytical model was developed from the perspective of society and the statutory health insurance was developed. Outcomes were the total number of newly detected true positive cases of amblyopia and the costs per newly detected true positive case of amblyopia. Strategies were screening of high-risk children up to the age of 1 year (ophthalmologists), screening of all children up to the age of 1 year (ophthalmologists), screening of all children aged 3 to 4 years (pediatricians or general practitioners), and screening of children aged 3 to 4 years visiting kindergarten (orthoptists). For the application example in a German setting, data from the published medical literature were used.Results.In the base-case analysis of the application example, screening high-risk children by opthalmologists had the lowest average cost per case detected but became dominated (less effective and more costly than an alternative) if a low (5.3%) probability of familial clustering of strabismus was assumed. Considering the various assumptions tested in the sensitivity analysis, screening of all children up to the age of 1 year by opthalmologists was the only strategy not dominated by others. Detection rates, including cases detected before screening, were between 72% and 78% for the strategies that screen for all children.Conclusions.The model suggests that in Germany, both from a cost-effectiveness and a pure effectiveness point of view, screening all children up to the age of 1 year by opthalmologists is the preferred strategy to detect amblyopia or amblyogenic factors. All strategies left a significant portion of children undetected.