Trachoma is an ocular infection caused by Chlamydia trachomatis that carries a huge public health burden as a leading cause of preventable blindness globally. We developed a model of the economic benefits of a potential vaccine. Factors that impact the efficacy of a vaccination program (such as the sensitivity and specificity of algorithms to identify high-risk individuals), and personal and environmental risk factors for trachoma affect the maximum vaccination and screening costs at which a vaccination program can achieve a positive net benefit. This model is useful for planning vaccine programs in areas with varying trachoma risk factors and endemicity.