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Pulmonary embolism (PE) is a significant cause of morbidity and mortality. The clinical diagnosis of PE can be quite challenging, necessitating a systematic, evidence-based, and cost-effective approach.A sensitive search strategy using keywords associated with PE diagnosis and economic evaluation was conducted. The libraries searched included MEDLINE, EMBASE, Health Technology Assessments, NHS Economic Evaluation Database, and the Cochrane Central Register of Clinical Trials. Studies were required to be a model-based cost-effectiveness analysis (CEA) for PE diagnosis. To be included, studies had to have evaluated both the cost and effectiveness of diagnostic algorithms. In addition, computed tomography (CT) had to have been a component in at least 1 possible algorithm. The characteristics of each CEA were extracted. In addition, the characteristics of CT pulmonary angiography were extracted (sensitivity, specificity, and cost). The most cost-effective strategy and its comparator were presented with the corresponding incremental cost-effectiveness ratio.Thirteen studies met our inclusion criteria. Costs were obtained using a variety of methods. Most studies measured effectiveness using a metric of survival, whereas 3 studies used quality-adjusted life years. Studies varied considerably in terms of the quality of economic evaluation. All but 1 study reported that computed tomographic pulmonary angiography (CTPA)—typically combined with ultrasound or D-dimer—was part of the most cost-effective algorithm.CEA is a useful tool for evaluating potential algorithms for PE diagnosis. Future CEAs would do well to include the use of magnetic resonance angiography and the potential for alternate diagnoses in diagnostic algorithms.